Updated on 2024/01/18

写真a

 
Hirata Yukiyo
 
Affiliation
Faculty of Medicine, Department of Hygiene and Public Health, Assistant Professor
Title
Assistant Professor
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Degree

  • 博士(医学) ( 日本医科大学 )

Research Areas

  • Life Science / Hygiene and public health

  • Life Science / Hygiene and public health

Research History

  • Nippon Medical School   Assistant Professor

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Papers

  • Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice

    Ying-Ji Li, Takako Shimizu, Yusuke Shinkai, Tomomi Ihara, Masao Sugamata, Katsuhito Kato, Maiko Kobayashi, Yukiyo Hirata, Hirofumi Inagaki, Makoto Uzuki, Toshio Akimoto, Masakazu Umezawa, Ken Takeda, Arata Azuma, Masayuki Yamamoto, Tomoyuki Kawada

    Biomedicines   8 ( 10 )   443 - 443   2020.10

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    Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    In the present study, we investigated the role of Nrf2 in airway immune responses induced by diesel exhaust (DE) inhalation in mice. C57BL/6J Nrf2+/+ and Nrf2−/− mice were exposed to DE or clean air for 8 h/day and 6 days/week for 4 weeks. After DE exposure, the number of neutrophils and macrophage inflammatory protein (MIP)-2 level in bronchoalveolar lavage fluid (BALF) and interleukin (IL)-17 level in the lung tissue increased in Nrf2−/− mice compared with Nrf2+/+ mice; however, the lack of an increase in the level of tumor necrosis factor (TNF)-α in the lung tissue in Nrf2+/+ mice and mild suppression of the level of TNF-α in Nrf2−/− mice were observed; the level of granulocyte macrophage colony-stimulating factor (GM-CSF) in the lung tissue decreased in Nrf2−/− mice than in Nrf2+/+ mice; the number of DE particle-laden alveolar macrophages in BALF were larger in Nrf2−/− mice than in Nrf2+/+ mice. The results of electron microscope observations showed alveolar type II cell injury and degeneration of the lamellar body after DE exposure in Nrf2−/− mice. Antioxidant enzyme NAD(P)H quinone dehydrogenase (NQO)1 mRNA expression level was higher in Nrf2+/+ mice than in Nrf2−/− mice after DE exposure. Our results suggested that Nrf2 reduces the risk of pulmonary disease via modulating the airway innate immune response caused by DE in mice.

    DOI: 10.3390/biomedicines8100443

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  • Nrf2 regulates the risk of a diesel exhaust inhalation-induced immune response during bleomycin lung injury and fibrosis in mice

    Ying Ji Li, Takako Shimizu, Yusuke Shinkai, Yukiyo Hirata, Hirofumi Inagaki, Ken Takeda, Arata Azuma, Masayuki Yamamoto, Tomoyuki Kawada

    International Journal of Molecular Sciences   18   2017.3

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    © 2017 by the authors. Licensee MDPI, Basel, Switzerland. The present study investigated the effects of diesel exhaust (DE) on an experimental model of bleomycin (BLM)-induced lung injury and fibrosis in mice. BLM was intravenously administered to both Nrf2+/+and Nrf2−/−C57BL/6J mice on day 0. The mice were exposed to DE for 56 days from 28 days before the BLM injection to 28 days after the BLM injection. Inhalation of DE induced significant inhibition of airway clearance function and the proinflammatory cytokine secretion in macrophages, an increase in neutrophils, and severe lung inflammatory injury, which were greater in Nrf2−/−mice than in Nrf2+/+mice. In contrast, inhalation of DE was observed to induce a greater increase of hydroxyproline content in the lung tissues and significantly higher pulmonary antioxidant enzyme mRNA expression in the Nrf2+/+mice than in Nrf2−/−mice. DE is an important risk factor, and Nrf2 regulates the risk of a DE inhalation induced immune response during BLM lung injury and fibrosis in mice.

    DOI: 10.3390/ijms18030649

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  • Nrf2 Regulates the Risk of a Diesel Exhaust Inhalation-Induced Immune Response during Bleomycin Lung Injury and Fibrosis in Mice Reviewed

    Ying-Ji Li, Takako Shimizu, Yusuke Shinkai, Yukiyo Hirata, Hirofumi Inagaki, Ken Takeda, Arata Azuma, Masayuki Yamamoto, Tomoyuki Kawada

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   18 ( 3 )   2017.3

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    The present study investigated the effects of diesel exhaust (DE) on an experimental model of bleomycin (BLM)-induced lung injury and fibrosis in mice. BLM was intravenously administered to both Nrf2(+/+) and Nrf2(-/-) C57BL/6J mice on day 0. The mice were exposed to DE for 56 days from 28 days before the BLM injection to 28 days after the BLM injection. Inhalation of DE induced significant inhibition of airway clearance function and the proinflammatory cytokine secretion in macrophages, an increase in neutrophils, and severe lung inflammatory injury, which were greater in Nrf2(-/-) mice than in Nrf2(+/+) mice. In contrast, inhalation of DE was observed to induce a greater increase of hydroxyproline content in the lung tissues and significantly higher pulmonary antioxidant enzyme mRNA expression in the Nrf2(+/+) mice than in Nrf2(-/-) mice. DE is an important risk factor, and Nrf2 regulates the risk of a DE inhalation induced immune response during BLM lung injury and fibrosis in mice.

    DOI: 10.3390/ijms18030649

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  • Effect of smoking prevention education using improved tobacco smoke collection method. Reviewed

    Katsumata M, Hirata K, Kobayashi M, Hirata Y, Inagaki H, Kawada T

    Nihon eiseigaku zasshi. Japanese journal of hygiene   69 ( 3 )   235 - 241   2014

  • Substrate specificity of human granzyme 3: Analyses of the P3-P2-P1 triplet using fluorescence resonance energy transfer substrate libraries Reviewed

    Yukiyo Hirata, Hirofumi Inagaki, Takako Shimizu, Tomoyuki Kawada

    BIOSCIENCE TRENDS   8 ( 2 )   126 - 131   2014

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:IRCA-BSSA  

    Granzyme 3 (Gr3) is known as a tryptase-type member of the granzyme family and exists in the granules of immunocompetent cells. Granule proteases including granzymes, are transported into the cytoplasm of tumor cells or virus-infected cells by perforin function, degrade cytoplasmic or nuclear proteins and subsequently cause the death of the target cells. Recently, although several substrates of Gr3 in vivo have been reported, these hydrolyzed sites were unclear or lacked consistency. Our previous study investigated the optimal amino acid triplet (P3-P2-P1) as a substrate for Gr3 using a limited combination of amino acids at the P2 and P3 positions. In the present study, new fluorescence resonance energy transfer (FRET) substrate libraries to screen P2 and P3 positions were synthesized, respectively. Using these substrate libraries, the optimal amino acid triplet was shown to be Tyr-Phe-Arg as a substrate for human Gr3. Moreover, kinetic analyses also showed that the synthetic substrate FRETS-YFR had the lowest Km value for human Gr3. A substantial number of membrane proteins possessed the triplet Tyr-Phe-Arg and some of them might be in vivo substrates for Gr3. The results might also be a great help for preparing specific inhibitors to manipulate Gr3 activity both in vitro and in vivo.

    DOI: 10.5582/bst.8.126

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  • EM, EM703 inhibit NF-kB activation induced by oxidative stress from diesel exhaust particle in human bronchial epithelial cells: Importance in IL-8 transcription Reviewed

    Ying-Ji Li, Takako Shimizu, Yukiyo Hirata, Hirofumi Inagaki, Hajime Takizawa, Arata Azuma, Tomoyuki Kawada, Isamu Sugawara, Shoji Kudoh, Toshiaki Sunazuka, Satoshi Omura

    PULMONARY PHARMACOLOGY & THERAPEUTICS   26 ( 3 )   318 - 324   2013.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

    Diesel exhaust particle (DEP) is the major components of PM2.5, and much attention has focused on PM2.5 in relation to adverse health effects, and many pulmonary diseases. In the present study, we used a human bronchial epithelial cell (HBEC) line to investigate the anti-inflammatory effects of erythromycin (EM) and EM703 - a new derivative of erythromycin without antibacterial effects on the expressions of IL-8 caused by DEP exposure. DEP showed a dose-dependent stimulatory effect on IL-8 product in HBEC. Increases of IL-8 expression by DEP stimulation were significantly blocked by both EM and EM703 pretreatment. Furthermore, NF-kappa B and Nrf2 activation, the antioxidant enzymes such as HO-1, NQO-1 mRNA expression were increased by DEP exposure and these increases were blocked by both of EM and EM703 pretreatment. Our results suggest that, EM and EM703 may have an inhibitory effect on expression inflammatory cytokines in HBEC induced by DEP not only as an anti-inflammation but also an antioxidant drug. EM and EM703 might contribute to chemical prevention of the risk of pulmonary diseases induced by oxidative stress from environmental pollutant, such as DEP. (C) 2013 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.pupt.2012.12.010

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  • Acute effects of walking in forest environments on cardiovascular and metabolic parameters Reviewed

    Qing Li, Toshiaki Otsuka, Maiko Kobayashi, Yoko Wakayama, Hirofumi Inagaki, Masao Katsumata, Yukiyo Hirata, YingJi Li, Kimiko Hirata, Takako Shimizu, Hiroko Suzuki, Tomoyuki Kawada, Takahide Kagawa

    EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY   111 ( 11 )   2845 - 2853   2011.11

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    We previously found that forest environments reduced stress hormones such as adrenaline and noradrenaline and showed the relaxing effect both in male and female subjects. In the present study, we investigated the effects of walking under forest environments on cardiovascular and metabolic parameters. Sixteen healthy male subjects (mean age 57.4 +/- 11.6 years) were selected after obtaining informed consent. The subjects took day trips to a forest park in the suburbs of Tokyo and to an urban area of Tokyo as a control in September 2010. On both trips, they walked for 2 h in the morning and afternoon on a Sunday. Blood and urine were sampled on the morning before each trip and after each trip. Blood pressure was measured on the morning (0800) before each trip, at noon (1300), in the afternoon (1600) during each trip, and on the morning (0800) after each trip. The day trip to the forest park significantly reduced blood pressure and urinary noradrenaline and dopamine levels and significantly increased serum adiponectin and dehydroepiandrosterone sulfate (DHEA-S) levels. Walking exercise also reduced the levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and urinary dopamine. Taken together, habitual walking in forest environments may lower blood pressure by reducing sympathetic nerve activity and have beneficial effects on blood adiponectin and DHEA-S levels, and habitual walking exercise may have beneficial effects on blood NT-proBNP levels.

    DOI: 10.1007/s00421-011-1918-z

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  • Effect of oral exposure to fenitrothion and 3-methyl-4-nitrophenol on splenic cell populations and histopathological alterations in spleen in Wistar rats Reviewed

    Qing Li, Maiko Kobayashi, Hirofumi Inagaki, Yukiyo Hirata, Shigeru Sato, Masamichi Ishizaki, Ai Okamura, Dong Wang, Tamie Nakajima, Michihiro Kamijima, Tomoyuki Kawada

    HUMAN & EXPERIMENTAL TOXICOLOGY   30 ( 7 )   665 - 674   2011.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SAGE PUBLICATIONS LTD  

    Fenitrothion (FNT) is used throughout the world as an insecticide in agriculture. To investigate the effect of FNT on the splenocytes and the underlying mechanism, FNT and its main metabolite, 3-methyl-4-nitrophenol (MNP), were administered orally to Wistar rats in daily doses of 0, 5 and 10 mg/kg, 4-5 days/week for 9 weeks. Splenocytes were harvested from control and exposed rats, and the following cell phenotypes were quantified by flow cytometry: (1) B cells (PE-CD45RA), (2) T cells (FITC-CD3), (3) T cell subsets (PE-CD4 and PerCP-CD8), (4) natural killer (NK) cells (FITC-CD161a), (5) macrophages (FITC-CD11b), and (6) granulocyte (PE-granulocyte). Body weight, weight of the spleen, and histopathological alterations of spleens were also examined. The percentage of splenic CD8+ T cells and the ratio of CD8/CD4 in the group receiving 10 mg/kg FNT, and the percentages of splenic CD3+ and CD8+ T cells in the group receiving 10 mg/kg MNP were significantly decreased compared with those in the controls. FNT exposure also significantly decreased the weight of the spleen and body weight. In addition, apoptotic lymphocytes in spleen were observed in FNT-exposed rats under transmission electron microscope. However, FNT and MNP exposures did not affect splenic NK cells, B cells, macrophages, and granulocytes. The above findings indicate that FNT and MNP may selectively affect splenic T cells in rats.

    DOI: 10.1177/0960327110377525

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  • Effects of subchronic inhalation exposure to ethyl tertiary butyl ether on splenocytes in mice. Reviewed

    Li Q, Kobayashi M, Inagaki H, Hirata Y, Shimizu T, Wang RS, Suda M, Kawamoto T, Nakajima T, Kawada T

    Int J Immunopathol Pharmacol   24 ( 4 )   837 - 847   2011

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  • A DAY TRIP TO A FOREST PARK INCREASES HUMAN NATURAL KILLER ACTIVITY AND THE EXPRESSION OF ANTI-CANCER PROTEINS IN MALE SUBJECTS

    Q. Li, M. Kobayashi, H. Inagaki, Y. Hirata, Y. J. Li, K. Hirata, T. Shimizu, H. Suzuki, M. Katsumata, Y. Wakayama, T. Kawada, T. Ohira, N. Matsui, T. Kagawa

    JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS   24 ( 2 )   157 - 165   2010.4

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    We previously reported that 2-night/3-day trips to forest parks enhanced human NK activity, the number of NK cells, and intracellular anti-cancer proteins in lymphocytes, and that this increased NK activity lasted for more than 7 days after the trip in both male and female subjects. In the present study, we investigated the effect of a day trip to a forest park on human INK activity in male subjects. Twelve healthy male subjects, aged 35-53 years, were selected after giving informed consent. The subjects experienced a day trip to a forest park in the suburbs of Tokyo. They walked for two hours in the morning and afternoon, respectively, in the forest park on Sunday. Blood and urine were sampled in the morning of the following day and 7 days after the trip, and the NK activity, numbers of NK and T cells, and granulysin, perforin, and granzyme A/B-expressing lymphocytes, the concentration of cortisol in blood samples, and the concentration of adrenaline in urine were measured. Similar measurements were made before the trip on a weekend day as the control. Phytoncide concentrations in the forest were measured. The day trip to the forest park significantly increased INK activity and the numbers of CD16(+) and CD56(+) NK cells, perforin, granulysin, and granzyme A/B-expressing NK cells and significantly decreased CD4(+) T cells, the concentrations of cortisol in the blood and adrenaline in urine. The increased INK activity lasted for 7 days after the trip. Phytoncides, such as isoprene, alpha-pinene, and beta-pinene, were detected in the forest air. These findings indicate that the day trip to the forest park also increased the NK activity, number of NK cells, and levels of intracellular anti-cancer proteins, and that this effect lasted for at least 7 days after the trip. Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity.

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  • Recombinant human progranzyme 3 expressed in Escherichia coli for analysis of its activation mechanism Reviewed

    Yukiyo Hirata, Hirofumi Inagaki, Tomoyuki Kawada

    MICROBIOLOGY AND IMMUNOLOGY   54 ( 2 )   98 - 104   2010.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL PUBLISHING, INC  

    Gr3 is reported to play an important role in defense against viral infection. Although it is known that Gr3 is synthesized as a proenzyme and activated in the cytotoxic granules of NK cells and CTL, the activation mechanism is not clearly understood. In an attempt to analyze the activation mechanism of human Gr3, a recombinant pro-Gr3 was expressed in the periplasm of E. coli and purified to homogeneity. On SDS-PAGE the recombinant pro-Gr3 showed a slightly higher molecular weight than the enzymatically active Gr3, because the former possesses a small propeptide at its N-terminal. The recombinant pro-Gr3 was enzymatically inactive. It could be activated by treatment with cathepsin C, which concomitantly decreased the molecular weight to that of active Gr3. The proteolytic reaction of cathepsin C did not continue after one dipeptide had been removed, indicating that the recombinant pro-Gr3 had the native conformation without any refolding process. The recombinant pro-Gr3 would be a valuable tool for analyzing the activation mechanism and exploring other activating enzymes besides cathepsin C.

    DOI: 10.1111/j.1348-0421.2009.00187.x

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  • EFFECT OF PHYTONCIDE FROM TREES ON HUMAN NATURAL KILLER CELL FUNCTION Reviewed

    Q. Li, M. Kobayashi, Y. Wakayama, H. Inagaki, M. Katsumata, Y. Hirata, K. Hirata, T. Shimizu, T. Kawada, B. J. Park, T. Ohira, T. Kagawa, Y. Miyazaki

    INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY   22 ( 4 )   951 - 959   2009.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BIOLIFE SAS  

    We previously reported that the forest environment enhanced human natural killer (NK) cell activity, the number of NK ceIls, and intracellular anti-cancer proteins in lymphocytes, and that the increased NK activity lasted for more than 7 days after trips to forests both in male and female subjects. To explore the factors in the forest environment that activated human NK cells, in the present study we investigate the effect of essential oils from trees on human immune function in twelve healthy male subjects, age 37-60 years, who stayed at an urban hotel for 3 nights from 7.00p.m. to 8.00a.m. Aromatic volatile substances (phytoncides) were produced by vaporizing Chamaecyparis obtusa (hinoki cypress) stem oil with a humidifier in the hotel room during the night stay. Blood samples were taken on the last day and urine samples were analysed every day during the stay. NK activity, the percentages of NK and T cells, and granulysin, perforin, granzyme A/B-expressing lymphocytes in blood, and the concentrations of adrenaline and noradrenaline in urine were measured. Similar control measurements were made before the stay on a normal working day. The concentrations of phytoncides in the hotel room air were measured. Phytoncide exposure significantly increased NK activity and the percentages of NK, perforin, granulysin, and granzyme A/B-expressing cells, and significantly decreased the percentage of T cells, and the concentrations of adrenaline and noradrenaline in urine. Phytoncides, such as alpha-pinene and beta-pinene, were detected in the hotel room air. These findings indicate that phytoncide exposure and decreased stress hormone levels may partially contribute to increased NK activity.

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  • [Evaluation of new saliva collection device for determination of salivary cotinine, cortisol, dehydroepiandrosterone and testosterone concentrations]. Reviewed

    Katsumata M, Hirata K, Inagaki H, Hirata Y, Kawada T

    Nihon eiseigaku zasshi. Japanese journal of hygiene   64 ( 4 )   811 - 816   2009.9

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    Language:Japanese   Publisher:The Japanese Society for Hygiene  

    Objectives: This study was conducted to examine the effectiveness of a new salivary collection device (φ10 mm × 25 mm) made of polypropylene and polyethylene polymers (Salisoft®).<br> Method: Experiment 1; We measured the absorption capacity of the new device by two methods. Next, we examined whether the device affected the pH of 0.1 M NaHCO3 solution (pH 8.7) and 0.1 M sodium phosphate buffer solution (pH 6.0). Experiment 2; We compared three saliva collection methods: by passive drool, using a cotton device (Salivette®), and using the new device. Saliva samples were collected from twelve men (average age, 31.5 ± 17.1 years). Saliva samples were assayed for cotinine, cortisol, dehydroepiandrosterone, and testosterone concentrations by enzyme immunoassay, and the pH of saliva samples were measured.<br> Results: After this device was put in the mouth for one minute, 1.28 ± 0.13 mL (mean ± SD, N = 6) of saliva samples were obtained. The mean pHs of saliva samples collected using Salisoft® and by passive drool did not differ significantly, whereas that of saliva samples collected with Salivette® was significantly low. Saliva samples collected with Salisoft® and those obtained by passive drool did not show significant differences in the concentrations of cotinine, cortisol, dehydroepiandrosterone, and testosterone. Moreover, significant positive correlations were noted between the concentrations in saliva samples collected with Salisoft® and those in saliva samples collected by passive drool.<br> Conclusion: This new device was shown to be suitable for saliva collection for the determination of the concentrations of cotinine and some steroids by enzyme immunoassay.<br>

    DOI: 10.1265/jjh.64.811

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  • Patterns in Self-Rated Health According to Age and Sex in a Japanese National Survey, 1989-2004 Reviewed

    Tomoyuki Kawada, Yoko Wakayama, Masao Katsumata, Hirofumi Inagaki, Toshiaki Otsuka, Yukiyo Hirata, Ying-Ji Li, Qing Li

    GENDER MEDICINE   6 ( 1 )   329 - 334   2009.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC  

    Background: Perceived good health or good self-rated health is considered to be a predictor of longer Survival and maintenance of good quality of life, which is a public health goal.
    Objective: This Study assessed trends in the percentage of self-rated poor health among Japanese residents, based on data from the National Comprehensive Survey of the Living Conditions of People on Health and Welfare.
    Methods: Results of the survey (which is conducted in Japan every 3 years to determine the living conditions of people receiving health and welfare services) were analyzed using multistage and stratified Cluster sampling Of households. Self-rated health was measured by response to the question, "Recently, would you say that in general your health has been good, fairly good, fair, fairly poor, or poor?" The trend in fairly poor or poor health status during the period from 1989 through 2004 was stratified by sex and age group.
    Results: The rates of response to the survey were 90.9% (246,892/271,588) in 1995 and 79.8% (220,836/276,682) in 2004. Target Subjects were aged &gt;= 20 years in each year of the Study. The prevalence of self-reported fairly poor or poor health was lowest in 1995 and then increased every year until 2001, when it appeared to reach a plateau. The prevalence of having fairly poor or poor health among women aged 35 to 44, 45 to 54, 55 to 64, and 65 to 74 years were as follows in 1995: 9.2%, 11.7%, 15.3%, and 19.8%, respectively. In 2004, the rates were 13.3%, 17.2%, 22.1%, and 31.7%, respectively. By comparison, the prevalence of self-reported fairly poor or poor health was 8.1%, 9.3%, 13.7%, and 17.9% among men aged 35 to 44, 45 to 54, 55 to 64, and 65 to 74 years, respectively, in 1995. In 2004, these rates were 12.8%, 14.8%, 19.0%, and 27.9%, respectively.
    Conclusions: In this survey, conducted every 3 years between 1989 and 2004 in Japanese households, older subjects had a greater prevalence of self-reported fairly poor or poor health than did Younger subjects. The proportion of respondents who described their health as poor or fairly poor was highest in 1995. Women generally had a greater prevalence of self-reported poor or fairly poor health. (Gend Med. 2009;6:329-334) (C) 2009 Excerpta Medica Inc.

    DOI: 10.1016/j.genm.2009.04.001

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  • [EM and EM703 suppress inflammatory cytokines formation by human respiratory epithelial cells provoked by diesel exhaust particles]. Reviewed

    Ri E, Shimizuq T, Hirata Y, Inagaki H, Takizawa H, Azuma A, Kawada T, Sugawara I, Kudo S, Sunazuka T, Omura S

    The Japanese journal of antibiotics   62 Suppl A   9 - 12   2009.3

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  • A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects. Reviewed

    Li Q, Morimoto K, Kobayashi M, Inagaki H, Katsumata M, Hirata Y, Hirata K, Shimizu T, Li YJ, Wakayama Y, Kawada T, Ohira T, Takayama N, Kagawa T, Miyazaki Y

    Journal of biological regulators and homeostatic agents   22   45 - 55   2008.1

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  • Visiting a forest, but not a city, increases human natural killer activity and expression of anti-cancer proteins Reviewed

    Q. Li, K. Morimoto, M. Kobayashi, H. Inagaki, M. Katsumata, Y. Hirata, K. Hirata, H. Suzuki, Y. J. Li, Y. Wakayama, T. Kawada, B. J. Park, T. Ohira, N. Matsu, T. Kagawa, Y. Miyazak, A. M. Krensky

    INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY   21 ( 1 )   117 - 127   2008.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BIOLIFE SAS  

    We previously reported that a forest bathing trip enhanced human NK activity, number of NK cells, and intracellular anti-cancer proteins in lymphocytes. In the present study, we investigated how long the increased NK activity lasts and compared the effect of a forest bathing trip on NK activity with a trip to places in a city without forests. Twelve healthy male subjects, age 35-56 years, were selected with informed consent. The subjects experienced a three-day/two-night trip to forest fields and to a city, in which activity levels during both trips were matched. On day 1, subjects walked for two hours in the afternoon in a forest field; and on day 2, they walked for two hours in the morning and afternoon, respectively, in two different forest fields; and on day 3, the subjects finished the trip and returned to Tokyo after drawing blood samples and completing the questionnaire. Blood and urine were sampled on the second and third days during the trips, and on days 7 and 30 after the trip, and NK activity, numbers of NK and T cells, and granulysin, perforin, and granzymes A/B-expressing lymphocytes in the blood samples,, and the concentration of adrenaline in urine were measured. Similar measurements were made before the trips on a normal working day as the control. Phytoncide concentrations in forest and city air were measured. The forest bathing trip significantly increased NK activity and the numbers of NK, perforin, granulysin, and granzyme A/B-expressing cells and significantly decreased the concentration of adrenaline in urine. The increased NK activity lasted for more than 7 days after the trip. In contrast, a city tourist visit did not increase NK activity, numbers of NK cells, nor the expression of selected intracellular anti-cancer proteins, and did not decrease the concentration of adrenaline in urine. Phytoncides, such as alpha-pinene and beta-pinene were detected in forest air, but almost not in city air. These findings indicate that a forest bathing trip increased NK activity, number of NK cells, and levels of intracellular anti-cancer proteins, and that this effect lasted at least 7 days after the trip. Phytoncides released from trees and decreased stress hormone may partially contribute to the increased NK activity.

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  • Healthy lifestyles are associated with higher levels of perforin, granulysin and granzymes A/B-expressing cells in peripheral blood lymphocytes Reviewed

    Qing Li, Kanehisa Morimoto, Ari Nakadai, Tianli Qu, Hiroki Matsushima, Masao Katsumata, Takako Shimizu, Hirofumi Inagaki, Yukiyo Hirata, Kimiko Hirata, Tomoyuki Kawada, Yuquan Lu, Kunio Nakayama, Alan M. Krensky

    PREVENTIVE MEDICINE   44 ( 2 )   117 - 123   2007.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Objective. It is well documented that natural killer (NK) cells provide host defense against tumors and viruses. We previously showed that lifestyle affects human NK and LAK activities. In order to explore the underlying mechanism, we investigated the effect of lifestyle on intracellular perforin, granulysin, and granzymes A/B in peripheral blood lymphocytes (PBL).
    Methods. 114 healthy male subjects, aged 20-59 years, from a large company in Osaka, Japan were selected with informed consent. The subjects were divided into groups reporting good, moderate, and poor lifestyles according to their responses on a questionnaire regarding eight health practices (cigarette smoking, alcohol consumption, sleeping hours, working hours, physical exercise, eating breakfast, balanced nutrition, and mental stress). Peripheral blood was taken, and numbers of NK, T, perform, granulysin, and granzymes A/B-expressing cells in PBL were measured by flow cytometry.
    Results. Subjects with good or moderate lifestyle showed significantly higher numbers of NK, and perform, granulysin, and granzymes A/B-expressing cells and a significantly lower number of T cells in PBL than subjects with poor lifestyle. Among the eight health practices, cigarette smoking, physical exercise, eating breakfast, and balanced nutrition significantly affect the numbers of NK, T cells, perform, granulysin, and/or granzymes A/B-expressing cells, and alcohol consumption significantly affects the number of granzyme A-expressing cells. On the other hand, mental stress, sleeping, and working hours had no effect on those parameters.
    Conclusions. Taken together, these findings indicate that poor lifestyle significantly decreases the numbers of NK, perforin, granulysin, and granzymes A/B-expressing cells in PBL. (c) 2006 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.ypmed.2006.08.017

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  • Expression of enzymatically active human granzyme 3 in Escherichia coli for analysis of its substrate specificity. Reviewed

    Hirata Y, Inagaki H, Shimizu T, Li Q, Nagahara N, Minami M, Kawada T

    Archives of biochemistry and biophysics   446 ( 1 )   35 - 43   2006.2

  • EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-β signaling in lung fibroblasts

    Ying Ji Li, Ying Ji Li, Arata Azuma, Jiro Usuki, Shinji Abe, Kuniko Matsuda, Toshiaki Sunazuka, Takako Shimizu, Yukiyo Hirata, Hirofumi Inagaki, Tomoyuki Kawada, Satoru Takahashi, Shoji Kudoh, Satoshi Omura

    Respiratory Research   7   2006.1

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    Background: Fourteen-membered ring macrolides have been effective in reducing chronic airway inflammation and also preventing lung injury and fibrosis in bleomycin-challenged mice via anti-inflammatory effects. EM703 is a new derivative of erythromycin (EM) without the bactericidal effects. We investigated the anti-inflammatory and antifibrotic effects of EM703 in an experimental model of bleomycin-induced lung injury and subsequent fibrosis in mice. Methods: Seven-week-old male ICR mice were used. All experiments used eight mice/group, unless otherwise noted in the figure legends. Bleomycin was administered intravenously to the mice on day 0. EM703 was orally administered daily to mice. All groups were examined for cell populations in the bronchoalveolar lavage (BAL) fluid and for induction of messenger RNA (mRNA) of Smad3 and Smad4 in the lung tissues by reverse transcriptase (RT)-polymerase chainreaction (PCR) on day 7. Fibroblastic foci were assessed histologically, and the hydroxyproline content was chemically determined in the lung tissues on day 28. We performed assay of proliferation and soluble collagen production, and examined the induction of mRNA of Smad3 and Smad4 by RTPCR in murine lung fibroblast cell line MLg2908. We also examined Smad3, Smad4 and phosphorylated Smad2/3 (p-Smad2/3) protein assay by western blotting in MLg2908. Results: Bleomycin-induced lung fibrosis, and the infiltration of macrophages and neutrophils into the airspace were inhibited by EM703. The expression of Smad3 and Smad4 mRNA was clearly attenuated by bleomycin, but was recovered by EM703. EM703 also inhibited fibroblast proliferation and the collagen production in lung fibroblasts induced by Transforming growth factor-beta (TGF-β). The expression of Smad3 and Smad4 mRNA in murine lung fibroblasts disappeared due to TGF-β, but was recovered by EM703. EM703 inhibited the expression of p-Smad2/3 and Smad4 protein in murine lung fibroblasts induced by TGF-β. Conclusion: These findings suggest that EM703 improves bleomycin-induced pulmonary fibrosis in mice by actions of anti-inflammation and regulation of TGF-β signaling in lung fibroblasts. © 2006 Li et al; licensee BioMed Central Ltd.

    DOI: 10.1186/1465-9921-7-16

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  • EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-beta signaling in lung fibroblasts Reviewed

    Li, YJ, Azuma, A, Usuki, J, Abe, S, Matsuda, K, Sunazuka, T, Shimizu, T, Hirata, Y, Inagaki, H, Kawada, T, Takahashi, S, Kudoh, S, Omura, S

    RESPIRATORY RESEARCH   7   0 - 0   2006.1

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    DOI: 10.1186/1465-9921-7-16

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  • Insomnia as a sequela of sarin toxicity several years after exposure in Tokyo subway trains Reviewed

    T Kawada, M Katsumata, H Suzuki, Q Li, H Inagaki, A Nakadai, T Shimizu, K Hirata, Y Hirata

    PERCEPTUAL AND MOTOR SKILLS   100 ( 3 )   1121 - 1126   2005.6

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    More than 5,000 passengers on Tokyo subway trains were injured with toxic chemicals including the nerve gas "sarin" on March 20, 1995. The purpose of this study was to identify the effect of satin exposure on insomnia in a cross-sectional study. A self-administered questionnaire concerning sleep-related items was distributed to victims of sarin exposure in October and November, 2003. Questionnaires were completed by 161 of the 163 participants (98.8%), who were selected from 1,500 subjects. Among them, the authors selected 75 women 30 to 69 years of age. Control participants were collected from inhabitants living in Maebachi City, Gunma Prefecture, Japan. For the younger exposed group (under 50 yr. of age), percentages of poor sleep, difficulty falling asleep, intermittent awakening, early morning awakening, a feeling of light overnight sleep, and insomnia were significantly higher than those for the control group. In contrast, the older exposed group (ages 50 to 69 years) had significantly higher prevalence of poor sleep, a feeling of light overnight sleep, and early morning awakening for the exposed group when compared with the control group. The high prevalence of insomnia and insomnia-related factors for victims especially under 50 years of age suggests a need for research on sleep quality after satin exposure. Although posttraumatic stress disorder is assumed to be a psychological effect of exposure to a toxic substance, a cause-and-effect relationship has not been established.

    DOI: 10.2466/pms.100.3c.1121-1126

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  • Elevated frequency of sister chromatid exchanges of lymphocytes in sarin-exposed victims of the Tokyo sarin disaster 3 years after the event Reviewed

    Qing Li, Yukiyo Hirata, Tomoyuki Kawada, Masayasu Minami

    Toxicology   201 ( 1-3 )   209 - 217   2004.9

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    We previously reported that the frequency of sister chromatid exchanges (SCEs) among victims of the Tokyo subway sarin disaster was significantly higher than that of controls 2-3 months after the disaster. It has been reported that the victims were also exposed to the by-products generated during sarin synthesis, i.e., diisopropyl methylphosphonate (DIMP), diethyl methylphosphonate (DEMP) and N,N-diethylaniline (DEA) during the disaster and we previously found that DIMP, DEMP and DEA induced a significant SCE increase in human lymphocytes in vitro. To monitor the genetic aftereffects of the sarin exposure, SCEs of peripheral blood lymphocytes were measured in fire fighters and police officers involved in the disaster 3 years after the event. We found that the frequency of SCEs was still significantly higher in the exposed subjects than the controls, suggesting a risk of the genetic aftereffects of the sarin exposure. We further found a significant positive correlation between the frequency of SCEs and the inhibition of serum cholinesterase activity in the exposed subjects, suggesting that the elevated frequency of SCEs is related to the sarin exposure. On the other hand, there was no significant difference in natural killer activity between the exposed and the controls. © 2004 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.tox.2004.04.014

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  • Immunotoxicity of N,N-diethylaniline in mice: Effect on natural killer activity, cytotoxic T lymphocyte activity, lymphocyte proliferation response and cellular components of the spleen Reviewed

    Qing Li, Yukiyo Hirata, Shunai Piao, Masayasu Minami

    Toxicology   150 ( 1-3 )   179 - 189   2000.9

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    We previously found that N,N-diethylaniline increased the frequency of sister chromatid exchange (SCE) of human lymphocytes to about five times that of the control value, and was as toxic as cyclophosphamide used as a positive control for SCE. To explore whether N,N-diethylaniline affects the function of lymphocytes, we evaluated its immunotoxicity using CBA/N mice. The mice were divided into four groups and received 0, 100, 200, or 400 mg/kg body weight of N,N-diethylaniline by subcutaneous injection. The following items were investigated on days 3 and 7 after injection: body weight, weight of spleen, number of splenocytes, natural killer (NK) and cytotoxic T lymphocyte (CTL) activities, and concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated lymphocyte proliferation using splenocytes. The following splenocyte phenotypes were also quantified by flow cytometry: (1) B cells
    (2) total T cells
    (3) CD4+ and CD8+ T cells
    (4) NK
    (5) macrophages and (6) nucleated erythrocytes. The splenic NK and CTL activities in exposed groups significantly decreased compared to the control in a dose-dependent manner and lymphocytes from the 200 and 400 mg/kg groups showed significantly higher spontaneous proliferation. The weight of the spleen and number of splenocytes were significantly higher in exposed groups than in the control. N,N-Diethylaniline also increased the percentages of macrophages, nucleated erythrocytes and B cells in the spleen. On the other hand, N,N-diethylaniline did not affect LPS-stimulated B cell and Con A-stimulated T cell proliferation, or the percentages of NK, total T, and CD4+ and CD8+ T cells in the spleen or the body weight of mice. The above findings indicated that N,N-diethylaniline selectively inhibited splenic NK and CTL activity and this inhibition was due to decreased NK and CTL functions, but not due to changes in the numbers of splenic NK and T cells. (C) 2000 Elsevier Science Ireland Ltd.

    DOI: 10.1016/S0300-483X(00)00247-X

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  • The by-products generated during sarin synthesis in the Tokyo sarin disaster induced inhibition of natural killer and cytotoxic T lymphocyte activity Reviewed

    Qing Li, Yukiyo Hirata, Shunai Piao, Masayasu Minami

    Toxicology   146 ( 2-3 )   209 - 220   2000.5

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    More than 5000 passengers on Tokyo subway trains were injured by the nerve gas, sarin and its by-products. Analysis of phosphor-carrying metabolites of sarin and its by-products in urine samples from the victims suggested that they were exposed not only to sarin, but also by-products generated during sarin synthesis, i.e. diisopropyl methylphosphonate (DIMP) and diethyl methylphosphonate (DEMP). We suspected genetic after-effects due to sarin by-products, thus, we checked the frequency of sister chromatid exchange (SCE) and found that SCE was significantly higher in the victims than in a control group, and that DIMP and DEMP significantly induced human lymphocyte SCE in vitro. In the present study, to explore whether DIMP and DEMP, which induced a high frequency of SCE of lymphocytes, also affected the lymphocyte functions, we examined the effect of DIMP and DEMP on splenic natural killer (NK) and splenic cytotoxic T lymphocyte (CTL) activity in mice, and NK activity of human lymphocytes in vitro. We found that DIMP and DEMP significantly inhibited NK and CTL activity in a dose-dependent manner. The inhibition induced by DIMP was stronger than that by DEMP. The effect of DIMP and DEMP on the splenic NK activity of mice was stronger than on the splenic CTL activity, and the human lymphocytes is more sensitive to DIMP and DEMP than the splenocytes of mice. (C) 2000 Elsevier Science Ireland Ltd.

    DOI: 10.1016/S0300-483X(00)00174-8

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Misc.

  • DEP曝露によるヒト気道上皮細胞遊走に及ぼすEM/EM703/EM900の影響

    小林麻衣子, 李英姫, 清水孝子, 平田幸代, 稲垣弘文, 川田智之

    日本衛生学雑誌(Web)   74 ( Supplement )   S165   2019.2

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  • DEP曝露によるヒト気道上皮細胞遊走に及ぼすEM/EM703/EM900の影響

    小林 麻衣子, 李 英姫, 清水 孝子, 平田 幸代, 稲垣 弘文, 川田 智之

    日本衛生学雑誌   74 ( Suppl. )   S165 - S165   2019.2

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  • HuH‐7細胞によるコリンエステラーゼの発現

    平田幸代, 稲垣弘文, 川田智之

    日本薬学会年会要旨集(CD-ROM)   139th   ROMBUNNO.23PO‐am287   2019

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  • 血清コリンエステラーゼのELISAに対するコリンエステラーゼ阻害剤の影響

    平田 幸代, 佐藤 美奈代, 稲垣 弘文, 川田 智之

    日本薬学会年会要旨集   138年会 ( 3 )   230 - 230   2018.3

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  • NK92MI細胞によるグランザイム3産生へのBrefeldin Aの影響

    稲垣 弘文, 平田 幸代

    日本薬学会年会要旨集   138年会 ( 3 )   168 - 168   2018.3

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  • ヒト血清コリンエステラーゼのホモ比活性の測定

    平田幸代, 稲垣弘文, 川田智之

    日本生化学会大会(Web)   91st   ROMBUNNO.3P‐315 (WEB ONLY)   2018

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  • NK92MI細胞が産生するグランザイム3の性状に与えるBrefeldin Aの影響

    稲垣弘文, 平田幸代

    日本生化学会大会(Web)   91st   ROMBUNNO.3P‐335 (WEB ONLY)   2018

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  • ヒト血清コリンエステラーゼに対するSandwich ELISAの確立

    平田 幸代, 佐藤 美奈代, 稲垣 弘文, 川田 智之

    生命科学系学会合同年次大会   2017年度   [2P - 1116]   2017.12

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  • NK92MI細胞が産生するGranzyme 3の性状

    稲垣 弘文, 平田 幸代

    生命科学系学会合同年次大会   2017年度   [2P - 0930]   2017.12

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  • NK92MI細胞が産生するGranzyme 3の性状

    稲垣 弘文, 平田 幸代

    生命科学系学会合同年次大会   2017年度   [2P - 0930]   2017.12

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  • ヒト血清コリンエステラーゼに対するSandwich ELISAの確立

    平田 幸代, 佐藤 美奈代, 稲垣 弘文, 川田 智之

    生命科学系学会合同年次大会   2017年度   [2P - 1116]   2017.12

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  • EFFECTS OF DIESEL EXHAUST PARTICLE IN HUMAN BRONCHIAL EPITHELIAL CELL MIGRATION AND THE INTRACELLULAR SIGNALING PATHWAY

    Ying-Ji Li, Maiko Kobayashi, Takako Shimizu, Yukiyo Hirata, Hirofumi Inagaki, Arata Azuma, Hajime Takizawa, Tomoyuki Kawada

    RESPIROLOGY   22   172 - 172   2017.11

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  • ラットグランザイム3の基質アミノ酸配列の検索

    平田 幸代, 稲垣 弘文

    日本薬学会年会要旨集   137年会 ( 3 )   129 - 129   2017.3

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  • Nrf2欠損マウスにおけるディーゼル排ガス吸入曝露のブレオマイシン肺障害病態への影響

    李 英姫, 清水 孝子, 新海 雄介, 平田 幸代, 稲垣 弘文, 武田 健, 吾妻 安良太, 山本 雅之, 川田 智之

    日本衛生学雑誌   72 ( Suppl. )   S210 - S210   2017.3

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  • ヒト気道上皮細胞遊走におけるディーゼル排気粒子の作用と細胞内シグナル伝達経路

    小林 麻衣子, 李 英姫, 清水 孝子, 平田 幸代, 稲垣 弘文, 川田 智之

    日本衛生学雑誌   72 ( Suppl. )   S222 - S222   2017.3

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  • NK92MI細胞によるGranzyme 3の産生

    稲垣 弘文, 平田 幸代

    日本薬学会年会要旨集   137年会 ( 3 )   128 - 128   2017.3

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  • DIESEL EXHAUST PARTICLE INDUCE EPITHELIAL-TO-MESENCHYMAL TRANSITION IN HUMAN BRONCHIAL EPITHELIAL CELL

    Y. J. Li, T. Shimizu, M. Kobayashi, Y. Hirata, H. Inagaki, A. Azuma, H. Takizawa, T. Kawada

    RESPIROLOGY   21   209 - 209   2016.11

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  • FRETSライブラリを用いたラットグランザイム3の基質特異性の解析

    平田 幸代, 稲垣 弘文

    日本生化学会大会プログラム・講演要旨集   89回   [3P - 179]   2016.9

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  • ラットグランザイム3の発現と基質特異性の解析

    平田 幸代, 稲垣 弘文, 川田 智之

    日本薬学会年会要旨集   136年会 ( 3 )   118 - 118   2016.3

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  • ラット末梢血単核球におけるグランザイム3の発現

    平田 幸代, 稲垣 弘文, 清水 孝子, 川田 智之

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   88回・38回   [3P1136] - [3P1136]   2015.12

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  • ヒト末梢血単核球によるグランザイム3産生へのBrefeldin Aの影響

    稲垣 弘文, 平田 幸代, 清水 孝子, 川田 智之

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   88回・38回   [3P1135] - [3P1135]   2015.12

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  • ヒト気道上皮細胞におけるディーゼル排気粒子の上皮間葉移行(EMT)誘発作用

    小林 麻衣子, 李 英姫, 清水 孝子, 平田 幸代, 稲垣 弘文, 川田 智之

    日本衛生学雑誌   70 ( Suppl. )   S185 - S185   2015.3

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  • ラット臓器におけるグランザイム3の発現

    平田 幸代, 稲垣 弘文, 清水 孝子, 川田 智之

    日本薬学会年会要旨集   135年会 ( 3 )   169 - 169   2015.3

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  • マイトゲン刺激によるヒト末梢血単核球のグランザイムA産生

    稲垣 弘文, 平田 幸代, 清水 孝子, 川田 智之

    日本生化学会大会プログラム・講演要旨集   87回   [3P - 461]   2014.10

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  • マイトゲン刺激下ヒト末梢血単核球によるグランザイム3の産生

    平田 幸代, 稲垣 弘文, 清水 孝子, 川田 智之

    日本生化学会大会プログラム・講演要旨集   87回   [3P - 460]   2014.10

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  • 改良したタバコ煙採取法を含む喫煙防止教育プログラムの検討

    勝又 聖夫, 平田 紀美子, 小林 麻衣子, 平田 幸代, 稲垣 弘文, 川田 智之

    日本衛生学雑誌   69 ( 3 )   235 - 241   2014.9

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    改良したタバコ煙採取法を含む喫煙防止教育プログラムについて検討した。改良したタバコ煙採取装置は、主流煙と副流煙を同時に採取でき、採取時にタバコ煙の曝露がない。また、有害ガスの検知を検知管法に加えて呈色反応を取り入れ、視覚的に有害ガスの存在を捉えることを追加した。加濃式社会的ニコチン依存度(KTSND)は、講義中に実習を行ったI群では、講義後及び1ヵ月後に得点が有意に低下したが、実習を行わないII群では、講義前後のみ有意差を認めた。アンケートで、I群では「タバコを吸うこと自体が病気である」、「タバコはストレスを解消する作用がある」、「タバコは喫煙者の頭の働きを高める」、「灰皿が置かれている場所は、喫煙できる場所である」で有意差を認めたが、II群では「灰皿が置かれている場所は、喫煙できる場所である」のみであった。

    DOI: 10.1265/jjh.69.235

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  • マイトゲン刺激下ヒト末梢血単核球によるグランザイムAの産生

    稲垣 弘文, 平田 幸代, 清水 孝子, 川田 智之

    日本薬学会年会要旨集   134年会 ( 3 )   174 - 174   2014.3

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  • コンカナバリンA刺激によるヒト末梢血単核球のグランザイム3産生

    平田 幸代, 稲垣 弘文, 清水 孝子, 川田 智之

    日本薬学会年会要旨集   134年会 ( 3 )   174 - 174   2014.3

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  • ヒト気管支上皮細胞においてディーゼル排気粒子は酸化ストレスにより上皮間葉転換を誘発する(Diesel exhaust particle induce epithelial-to-mesenchymal transition by oxidative stress in human bronchial epithelial cell)

    李 英姫, 清水 孝子, 平田 幸代, 稲垣 弘文, 川田 智之, 吾妻 安良太, 滝澤 始, 工藤 翔二

    日本呼吸器学会誌   3 ( 増刊 )   263 - 263   2014.3

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  • 血中セリンプロテアーゼ阻害蛋白のヒトグランザイム3およびグランザイムAへの影響

    平田 幸代, 稲垣 弘文, 川田 智之

    日本生化学会大会プログラム・講演要旨集   86回   1P - 165   2013.9

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  • Diesel exhaust particle induce epithelial-to-mesenchymal transition by oxidative stress in human bronchial epithelial cell

    Ying-Ji Li, Takako Shimizu, Yukiyo Hirata, Hirofumi Inagaki, Yusuke Shinkai, Ken Takeda, Arata Azuma, Hajime Takizawa, Xiangde Liu, Tomoyuki Kawada, Shoji Kudoh

    EUROPEAN RESPIRATORY JOURNAL   42   2013.9

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  • 唾液中Chromogranin AのEIA測定法における唾液採取器具の検討

    勝又 聖夫, 平田 紀美子, 小林 麻衣子, 平田 幸代, 稲垣 弘文, 川田 智之

    日本衛生学雑誌   68 ( Suppl. )   S219 - S219   2013.3

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  • Nrf2欠損マウスにおけるディーゼル排気粒子曝露のプレオマイシン気道炎症病態への影響

    李 英姫, 清水 孝子, 平田 幸代, 稲垣 弘文, 新海 雄介, 武田 健, 吾妻 安良太, 滝澤 始, 山本 雅之, 川田 智之, 工藤 翔二

    日本呼吸器学会誌   2 ( 増刊 )   176 - 176   2013.3

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  • Nrf2欠損マウスを用いたディーゼル排気粒子のブレオマイシン気道炎症病態への影響

    李 英姫, 清水 孝子, 平田 幸代, 稲垣 弘文, 新海 雄介, 武田 健, 吾妻 安良太, 滝澤 始, 山本 雅之, 川田 智之

    日本衛生学雑誌   68 ( Suppl. )   S214 - S214   2013.3

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  • Effect of phytoncides from forest environments on immune function

    Qing Li, Maiko Kobayashi, Hirofumi Inagaki, Yoko Wakayama, Masao Katsumata, Yukiyo Hirata, Yingji Li, Kimiko Hirata, Takako Shimizu, Ari Nakadai, Tomoyuki Kawada

    Forest Medicine   159 - 169   2012.12

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    We previously reported that the forest environment enhanced human natural killer (NK) activity, the number of NK cells, and intracellular levels of anti-cancer proteins in lymphocytes, and that the increased NK activity lasted for more than 7 days after trips to forests in both male and female subjects. To explore the factors in the forest environment that activated human NK cells, we investigated the effect of essential oils from trees on human immune function both in vitro and in vivo. In the in vitro study, we investigatedthe effect of 8 kinds of phytoncides (wood essential oil) on NK activity and the expression of perforin, granzyme A (GrA) and granulysin (GRN) in human NK cells. We found that phytoncides significantly increased NK activity in a dose-dependent manner and significantly increased the expression of perforin, GrA and GRN. The phytoncides also partially restored NK activity and perforin, GrA and GRN levels reduced by DDVP. We found that pretreatment with phytoncides partially prevented the DDVP-induced inhibition of NK activity. These findings suggest that phytoncides can increase human NK activity. In the in vivo study, twelve healthy male subjects, aged 37-60 years, were put up in urban hotel for 3 nights. Aromatic volatile substances (phytoncides) were produced by vaporizing Chamaecyparis obtusa stem oil with a humidifier in the hotel room during the night. Blood was sampled on the last day and urine was sampled every day during the stay. Similar control measurements were made before the stay on a normal working day. The concentrations of phytoncides in hotel room air were measured. Phytoncide exposure significantly increased NK activity and the numbers of NK, perforin, GRN, and GrA/B-expressing cells, and significantly decreased the concentrations of adrenaline and noradrenaline in urine. These findings indicate that phytoncide exposure and decreased stress hormone levels partially contribute to increased NK activity. © 2013 by Nova Science Publishers, Inc. All rights reserved.

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  • Effect of forest environments on psychological response evaluated by the POMS test

    Qing Li, Maiko Kobayashi, Yoko Wakayama, Hirofumi Inagaki, Masao Katsumata, Yukiyo Hirata, Yingji Li, Kimiko Hirata, Takako Shimizu, Hiroko Suzuki, Toshiaki Otsuka, Tomoyuki Kawada

    Forest Medicine   137 - 146   2012.12

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    We used the POMS test to investigate the psychological effects of trips to a forest in both males and females. Methods: Three experiments were conducted. 1) Twelve healthy male subjects, aged 37-55 years, and 13 healthy female subjects, aged 25-43 years, experienced a threeday/ two-night trip to forest fields. On day 1, subjects walked for two hours in the afternoon in a field; and on day 2, they walked for two hours each in the morning and afternoon, at two different fields. 2) Sixteen healthy males, aged 36-77 years, experienced day trips to an urban area and a forest park in the suburbs of Tokyo. They walked for two hours each in the morning and afternoon, in the forest park/ urban area on a Sunday. 3) 53 and 98 subjects experienced a 2-hour walk in a forest field and a city park, respectively. The POMS test was conducted before, during, and after the trip/walk. Results: The three-day excursion significantly increased the score for vigor and decreased the scores for anxiety, depression and anger in males; and significantly increased the score for vigor and decreased the scores for anxiety, depression, anger, fatigue, and confusion in females. The day trip to the forest park or urban area also significantly decreased the scores for anxiety, depression, anger, and confusion; however, only the trip to the forest park significantly increased the score for vigor and decreased the scores for fatigue in male subjects. The 2-hour walk in a city park with a good density of trees or in a forest field also significantly increased the score for vigor and decreased the scores for anxiety, depression, anger, fatigue, and confusion in both male and female subjects. Conclusions: Walking significantly decreased the scores for anxiety, depression, anger, fatigue and confusion; however only walking in forest fields, not in a city area, significantly increased the score for vigor. © 2013 by Nova Science Publishers, Inc. All rights reserved.

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  • Effect of forest bathing on sleep and physical activity

    Tomoyuki Kawada, Ari Nakadai, Hirofumi Inagaki, Masao Katsumata, Takako Shimizu, Yukiyo Hirata, Kimiko Hirata, Hiroko Suzuki

    Forest Medicine   105 - 109   2012.12

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    In order to explore the effect of a forest trip on human sleep, we performed continuous monitoring with an accelerometer, including during forest visits. Methods: Twelve healthy male office workers in Tokyo, aged 37 to 55 years old, were selected for the study after obtaining their informed consent. The subjects undertook a three-day/two-night trip to three different forest fields. On the first day, they walked for two hours in the afternoon in a forest field; on the second day, they walked for two hours in the morning and in the afternoon, respectively, in two different forest fields. An accelerometer was used to monitor the duration of sleep and the daily physical activity level. Results: Significant increase of the sleep time during the forest bathing trip was recognized as compared with that noted before the trip. In addition, there was also a significant increase of the daily physical activity during the trip as compared with that after the trip. Conclusions: The authors speculate that the forest bathing trip might have had a beneficial effect on the sleep time, irrespective of the daily physical activity level.© 2013 by Nova Science Publishers, Inc. All rights reserved.

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  • Effects of forest environments on cardiovascular and metabolic parameters

    Qing Li, Toshiaki Otsuka, Maiko Kobayashi, Yoko Wakayama, Hirofumi Inagaki, Masao Katsumata, Yukiyo Hirata, Yingji Li, Kimiko Hirata, Takako Shimizu, Hiroko Suzuki, Tomoyuki Kawada, Takahide Kagawa

    Forest Medicine   117 - 136   2012.12

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    To investigate the effects of forest environments on cardiovascular and metabolic parameters, sixteen healthy male subjects (mean age: 57.4±11.6 years) were selected after obtaining informed consent. The subjects took day trips to a forest park in the suburbs of Tokyo and to an urban area of Tokyo as a control in September 2010. On both trips, they walked for two hours in the morning and afternoon on a Sunday. Blood and urine were sampled on the morning before each trip and after each trip. Blood pressure was measured on the morning (0800) before each trip, at noon (1300), in the afternoon (1600) during each trip, and on the morning (0800) after each trip. The day trip to the forest park significantly reduced blood pressure and urinary noradrenaline and dopamine levels and significantly increased serum adiponectin and dehydroepiandrosterone sulfate (DHEA-S) levels. Walking exercise also reduced the levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), blood HbA1c and urinary dopamine. However, forest environments did not affect the levels of triglycerides, total Cho, LDL-Cho, HDL-Cho, RLP-Cho, insulin, or hs-CRP in serum, blood glucose, or hematological parameters. Taken together, habitual walking in forest environments may lower blood pressure by reducing sympathetic nerve activity and have beneficial effects on blood adiponectin and DHEA-S levels, and habitual walking exercise may have beneficial effects on blood NT-proBNP levels.© 2013 by Nova Science Publishers, Inc. All rights reserved.

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  • 抗ヒトGranzyme 3モノクローナル抗体による酵素活性の上昇

    稲垣 弘文, 平田 幸代, 清水 孝子, 川田 智之

    日本生化学会大会プログラム・講演要旨集   85回   3P - 277   2012.12

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  • FRET基質を用いたヒトGranzyme 3の反応速度論的解析

    平田 幸代, 稲垣 弘文, 清水 孝子, 川田 智之

    日本生化学会大会プログラム・講演要旨集   85回   3P - 278   2012.12

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  • 亜慢性ETBE吸入ばく露によるマウス脾臓細胞への影響

    李 卿, 小林 麻衣子, 稲垣 弘文, 平田 幸代, 平田 紀美子, 清水 孝子, 王 瑞生, 須田 恵, 川田 智之

    労働安全衛生総合研究所特別研究報告   ( 42 )   163 - 170   2012.11

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    ETBEは自動車のバイオ燃料として使用されており,現在その使用量がそれほど多くないが,増加している傾向である.本研究はETBEによる免疫毒性を検討する目的でまずはETBEによる脾臓細胞への影響を検討した.C57BL/6Jと129/SV雄性マウスは6時間/日,5日/週のスケジュールで0ppm(対照),500ppm,1,750ppmおよび5,000ppmのETBEにそれぞれ6と13週間吸入ばく露し,最終ばく露の20時間後に解剖して脾臓を採取し,脾細胞を調製し,Flow cytometry法を用いて以下の脾細胞表面マーカーを測定・解析した.(1)T細胞(PerCP-Cy5.5-CD3e),(2)T細胞サブセット(FITC-CD4とPE-CD8a),(3)B細胞(PerCP-Cy5.5-CD45R/B220),(4)NK細胞(PE-NK1.1)及び(5)マクロファージ(FITC-CD11b).末梢血Hb濃度,赤血球数,白血球数,血小板,体重及び脾臓対体重比も測定した.その結果,ETBEばく露は一時的に末梢血Hb濃度,赤血球数を増加させたが,体重及び脾臓対体重比には影響を及ぼさなかった.ETBEばく露は,ばく露量に依存して脾臓CD3+T細胞,CD4+T細胞,CD8+T細胞,CD4+T細胞陽性率及びCD4+/CD8+T細胞比を有意に減少させることが明らかとなった.一方でETBEばく露は,脾臓NK細胞,B細胞,マクロファージ及び脾臓細胞総数に影響を及ぼさなかった.結論として本研究は,ETBE単独ばく露による免疫毒性を初めて明らかにしたと共に,ETBEが選択的にマウス脾臓T細胞数を減少させることが判明した.(著者抄録)

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  • Nrf2 is closely related to enhance bleomycin induced airway inflammatory responses caused by diesel exhaust particles in mice

    Ying-Ji Li, Tkako Shimizu, Yukiyo Hirata, Hirofumi Inagaki, Yusuke Shinkai, Ken Takeda, Arata Azuma, Hajime Takizawa, Yamamoto Masayuki, Tomoyuki Kawada, Shoji Kudoh

    EUROPEAN RESPIRATORY JOURNAL   40   2012.9

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  • 抗ヒトGranzyme 3モノクローナル抗体の酵素活性への影響

    稲垣 弘文, 平田 幸代, 清水 孝子, 川田 智之

    日本薬学会年会要旨集   132年会 ( 3 )   194 - 194   2012.3

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  • FRET基質ライブラリを用いたヒトGranzyme 3とGranzyme Aの活性比較

    平田 幸代, 稲垣 弘文, 清水 孝子, 川田 智之

    日本薬学会年会要旨集   132年会 ( 3 )   193 - 193   2012.3

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  • ディーゼル排気粒子の気道上皮細胞の遊走、および上皮間葉移行(EMT)に及ぼす影響

    李 英姫, 清水 孝子, 平田 幸代, 稲垣 弘文, 新海 雄介, 吾妻 安良太, 滝澤 始, 武田 健, 川田 智之, 工藤 翔二

    日本衛生学雑誌   67 ( 2 )   284 - 284   2012.2

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  • 森林浴による気分への影響

    小林 麻衣子, 李 卿, 大塚 俊昭, 平田 幸代, 平田 紀美子, 五月女 孝子, 川田 智之

    日本衛生学雑誌   67 ( 2 )   299 - 299   2012.2

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  • ヒト前駆体型Granzyme 3に特異的なsandwich ELISAの確立

    稲垣 弘文, 平田 幸代, 清水 孝子, 川田 智之

    日本生化学会大会プログラム・講演要旨集   84回   3P - 0202   2011.9

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  • ヒトGranzyme 3の基質アミノ酸配列の検索

    平田 幸代, 稲垣 弘文, 清水 孝子, 川田 智之

    日本生化学会大会プログラム・講演要旨集   84回   3P - 0203   2011.9

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  • 健常男性におけるウォーキングがNT-proBNP値におよぼす影響の検討

    大塚 俊昭, 李 卿, 小林 麻衣子, 若山 葉子, 稲垣 弘文, 勝又 聖夫, 平田 幸代, 李 英姫, 平田 紀美子, 清水 孝子, 鈴木 博子, 川田 智之, 香川 隆英

    成人病と生活習慣病   41 ( 5 )   620 - 621   2011.5

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  • ヒトGranzyme 3の基質アミノ酸配列の検索

    平田 幸代, 稲垣 弘文, 清水 孝子, 川田 智之

    日本薬学会年会要旨集   131年会 ( 3 )   157 - 157   2011.3

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  • Nrf2欠損マウスにおけるブレオマイシン肺線維症病態

    李 英姫, 清水 孝子, 平田 幸代, 稲垣 弘文, 吾妻 安良太, 滝澤 始, 高橋 智, 山本 雅之, 川田 智之, 工藤 翔二

    日本呼吸器学会雑誌   49 ( 増刊 )   243 - 243   2011.3

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  • ディーゼル排気粒子のマウスブレオマイシン肺線維症病態への影響

    李 英姫, 清水 孝子, 平田 幸代, 稲垣 弘文, 新海 雄介, 武田 健, 川田 智之, 吾妻 安良太, 滝澤 始, 工藤 翔二

    日本衛生学雑誌   66 ( 2 )   459 - 459   2011.2

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  • 日帰り森林浴による血圧への影響

    李 卿, 大塚 俊昭, 小林 麻衣子, 若山 葉子, 稲垣 弘文, 勝又 聖夫, 平田 幸代, 李 英姫, 平田 紀美子, 清水 孝子, 伊藤 博子, 川田 智之, 香川 隆英

    日本衛生学雑誌   66 ( 2 )   379 - 379   2011.2

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  • 日帰り森林浴と都市部観光によるリラックス効果の比較

    小林 麻衣子, 李 卿, 若山 葉子, 稲垣 弘文, 大塚 俊昭, 勝又 聖夫, 平田 幸代, 李 英姫, 平田 紀美子, 五月女 孝子, 伊藤 博子, 川田 智之, 香川 隆英

    日本衛生学雑誌   66 ( 2 )   450 - 450   2011.2

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  • 健常男性におけるウォーキングがNT-proBNP値におよぼす影響の検討

    大塚 俊昭, 李 卿, 香川 隆英, 小林 麻衣子, 若山 葉子, 稲垣 弘文, 勝又 聖夫, 平田 幸代, 李 英姫, 平田 紀美子, 清水 孝子, 鈴木 博子, 川田 智之

    日本成人病(生活習慣病)学会会誌   37   80 - 80   2011.1

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  • Nrf2 Is Closely Related To Bleomycin Induced Airway Inflammation And Lung Fibrosis In Mice

    Y. -J. Li, T. Shimizu, Y. Hirata, H. Inagakia, A. Azuma, H. Takizawa, S. Takahashi, M. Yamamoto, T. Kawada, S. Kudoh

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   183   2011

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  • Diesel Exhaust Particle Exposure Influences Bleomycin-Induced Lung Fibrosis in Mice

    Ying-Ji Li, Takako Shimizu, Yukiyo Hirata, Hirofumi Inagaki, Yusuke Shinkai, Ken Takeda, Tomoyuki Kawada, Arata Azuma, Hajime Takizawa, Shoji Kudoh

    CANCER CYTOPATHOLOGY   118 ( 5 )   364 - 364   2010.10

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  • 13週間ETBE慢性吸入曝露によるマウス脾臓細胞への影響

    李 卿, 稲垣 弘文, 平田 幸代, 川田 智之, 須田 恵, 王 瑞生

    産業衛生学雑誌   52 ( 臨増 )   477 - 477   2010.5

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  • 日帰り森林浴による生体免疫機能への効果

    李 卿, 小林 麻衣子, 稲垣 弘文, 平田 幸代, 李 英姫, 平田 紀美子, 清水 孝子, 鈴木 博子, 勝又 聖夫, 若山 葉子, 川田 智之, 大平 辰朗, 松井 直之, 香川 隆英

    日本衛生学雑誌   65 ( 2 )   368 - 368   2010.4

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  • 日帰り森林浴によるリラックス効果

    小林 麻衣子, 李 卿, 若山 葉子, 勝又 聖夫, 稲垣 弘文, 平田 幸代, 李 英姫, 平田 紀美子, 五月女 孝子, 伊藤 博子, 川田 智之, 香川 隆英

    日本衛生学雑誌   65 ( 2 )   314 - 314   2010.4

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  • ニコチン、コチニン同時測定のために開発した新しい唾液採取器具を用いた唾液中ステロイドホルモン類の測定

    平田 紀美子, 勝又 聖夫, 稲垣 弘文, 平田 幸代, 川田 智之

    日本薬学会年会要旨集   130年会 ( 3 )   252 - 252   2010.3

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  • Lymphokine-activated killer(LAK)細胞によるGranzyme3の産生

    稲垣 弘文, 平田 幸代, 清水 孝子, 小林 麻衣子, 川田 智之

    日本薬学会年会要旨集   130年会 ( 3 )   205 - 205   2010.3

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  • 活性型ヒトGranzyme3に特異的なsandwich ELISAの確立

    平田 幸代, 稲垣 弘文, 清水 孝子, 川田 智之

    日本薬学会年会要旨集   130年会 ( 3 )   205 - 205   2010.3

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  • 新しい素材を用いた唾液採取器具による唾液中のコチニン、コルチゾール、デヒドロエピアンドロステロン及びテストステロンの測定

    勝又 聖夫, 平田 紀美子, 稲垣 弘文, 平田 幸代, 川田 智之

    日本衛生学雑誌   64 ( 4 )   811 - 816   2009.9

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    コットン以外の素材を用いた唾液採取器具(サリソフト及びサリキッズ)を考案し、その考案したサリソフト吸収体の唾液の採取量や唾液のpHの変動への影響等の基礎的な検討を行った。さらに、喫煙の曝露評価に用いられている唾液中Cotinineや唾液に存在しているステロイドホルモンであるCortisol、DHEA及びTestosteroneの測定を行い、考案した唾液吸収体の有用性の検討を行った。ポリプロピレンとポリエチレンの重合体を素材とした吸収体を用いた唾液採取器具サリソフトは、唾液が充分に採取でき、唾液pHの変動に影響を及ぼさず、唾液中のCotinineやCortisol等のステロイドホルモン等の測定に適していることが示された。

    DOI: 10.1265/jjh.64.811

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  • 活性型ヒトGranzyme 3に対する高感度sandwich ELISA

    平田 幸代, 稲垣 弘文, 清水 孝子, 川田 智之

    日本生化学会大会プログラム・講演要旨集   82回   3P - 696   2009.9

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  • ヒト末梢血Granzyme 3陽性細胞のFlow Cytometry解析

    稲垣 弘文, 平田 幸代, 清水 孝子, 小林 麻衣子, 李 卿, 川田 智之

    日本生化学会大会プログラム・講演要旨集   82回   3P - 695   2009.9

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  • Effect of oral exposure to fenitrothion and 3-methyl-4-nitrophenol on immune function in Wistar rats

    Qing Li, Maiko Kobayashi, Hirofumi Inagaki, Yukiyo Hirata, Masamichi Ishizaki, Ai Okamura, Dong Wang, Tamie Nakajima, Michihiro Kamijima, Tomoyuki Kawada

    TOXICOLOGY LETTERS   189   S163 - S163   2009.9

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    DOI: 10.1016/j.toxlet.2009.06.677

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  • ヒノキ精油によるリラックス効果

    小林 麻衣子, 李 卿, 若山 葉子, 勝又 聖夫, 稲垣 弘文, 平田 幸代, 平田 紀美子, 五月女 孝子, 川田 智之, 宮崎 良文

    日本衛生学雑誌   64 ( 2 )   418 - 418   2009.3

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  • 活性型ヒトGranzyme 3に対するsandwich ELISA

    平田 幸代, 稲垣 弘文, 清水 孝子, 川田 智之

    日本薬学会年会要旨集   129年会 ( 3 )   156 - 156   2009.3

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  • ヒト末梢血リンパ球におけるGranzyme 3の分布

    稲垣 弘文, 平田 幸代, 清水 孝子, 小林 麻衣子, 李 卿, 川田 智之

    日本薬学会年会要旨集   129年会 ( 3 )   157 - 157   2009.3

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  • Fenitrothion(FNT)と3-methyl-4-nitrophenol(MNP)の経口曝露によるラット免疫機能への影響

    李 卿, 稲垣 弘文, 平田 幸代, 岡村 愛, 王 棟, 那須 民江, 上島 通浩, 川田 智之

    産業衛生学雑誌   51 ( 臨増 )   281 - 281   2009.3

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  • Erythromycin (EM)center dot EM703 Inhibits Inflammatory Cytokine Production in Human Bronchial Epithelial Cells Caused by Diesel Exhaust Particle.

    Y. -J. Li, T. Shimizu, Y. Hirata, H. Inagaki, H. Takizawa, A. Azuma, T. Kawada, I. Sugawara, S. Kudoh, T. Sunazuka, S. Omura

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   179   2009

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  • 活性型ヒトGranzyme 3に対するモノクローナル抗体の作製

    稲垣 弘文, 平田 幸代, 李 卿, 小林 麻衣子, 清水 孝子, 川田 智之

    日本薬学会年会要旨集   128年会 ( 3 )   64 - 64   2008.3

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  • 森林浴によるリラックス効果

    小林 麻衣子, 李 卿, 稲垣 弘文, 勝又 聖夫, 平田 幸代, 李 英姫, 平田 紀美子, 五月女 孝子, 若山 葉子, 川田 智之

    日本衛生学雑誌   63 ( 2 )   379 - 379   2008.3

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  • 森林浴による看護師のストレス軽減

    李 卿, 稲垣 弘文, 勝又 聖夫, 平田 幸代, 川田 智之, 森本 兼曩

    産業衛生学雑誌   50 ( 臨増 )   F309 - F309   2008.3

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  • 職域における労働者の生活習慣と気分障害の関連性

    川田 智之, 大塚 俊昭, 稲垣 弘文, 李 卿, 勝又 聖夫, 平田 幸代

    産業衛生学雑誌   ( 80回CD-ROM抄録集 )   P2057 - P2057   2007.4

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  • 森林浴によるリラックス効果 一般旅行との比較

    小林 麻衣子, 李 卿, 稲垣 弘文, 勝又 聖夫, 平田 幸代, 平田 紀美子, 伊藤 博子, 李 英姫, 若山 葉子, 川田 智之

    日本衛生学雑誌   62 ( 2 )   542 - 542   2007.3

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  • Forest bathing enhances human natural killer activity and expression of anti-cancer proteins (森林浴は抗ガンタンパクの発現とNK活性を増強する)

    Qing,Li, 日本医科大, Kanehisa,Morimoto, 、Ari,Nakadai, 日本医科, Hirofumi,Inagaki, 日本医科大, Masao,Katsumata, Takako,Shimizu, Yukiyo,Hirata, Kimiko,Hirata, 日本医科, Hiroko,Suzuki, Yoshifumi,Miyazaki(宮崎良, Takahide,Kagawa, Yashuhiro,Koyama, 長野県林業総合セ, Tatsuro,Ohira, 大平, Norimasa,Takayama, Tomoyuki,Kawada, 本医

    International Journal of Immunopathology & Pharmacology   20 ( 2 Suppl 2 )   3 - 8   2007

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  • ライフスタイルによるヒトNK、T細胞及びリンパ球内Granulysin,Perforin,Granzyme A/Bへの影響

    李 卿, 中台 亜里, 屈 田力, 松島 弘樹, 勝又 聖夫, 清水 孝子, 稲垣 弘文, 平田 幸代, 平田 紀美子, 川田 智之, 呂 玉泉, 中山 邦夫, Krensky AM, 森本 兼曩

    産業衛生学雑誌   48 ( 臨増 )   np316 - np316   2006.4

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    DOI: 10.1539/sangyoeisei.KJ00004429580

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  • リコンビナントヒトGranzyme Aの発現とその性質

    稲垣 弘文, 平田 幸代, 清水 孝子, 川田 智之

    日本薬学会年会要旨集   126年会 ( 3 )   56 - 56   2006.3

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  • セリンプロテアーゼ阻害剤のヒトGranzyme 3及びAへの影響

    平田 幸代, 稲垣 弘文, 川田 智之

    日本薬学会年会要旨集   126年会 ( 3 )   56 - 56   2006.3

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  • FRETSライブラリを用いたヒトGranzyme 3の基質特異性の解析

    平田 幸代, 稲垣 弘文, 清水 孝子, 李 卿, 永原 則之, 川田 智之

    日本薬学会年会要旨集   125年会 ( 3 )   40 - 40   2005.3

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  • 職域における「死の3ないし4重奏」危険因子保有者割合からみた労災保険二次健診の意義

    川田 智之, 中台 亜里, 平田 幸代, 勝又 聖夫, 李 卿, 稲垣 弘文, 永原 則之

    産業衛生学雑誌   46 ( 臨増 )   371 - 371   2004.3

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  • 抗ヒトGranzyme 3モノクローナル抗体の作製

    平田 幸代, 稲垣 弘文, 清水 孝子, 李 卿, 川田 智之

    日本薬学会年会要旨集   124年会 ( 3 )   159 - 159   2004.3

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  • Serine protease inhibitorのヒトGranzyme 3活性への影響

    平田 幸代, 李 卿, 稲垣 弘文, 永原 則之, 川田 智之

    日本薬学会年会要旨集   124年会 ( 3 )   159 - 159   2004.3

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  • RecombinantヒトGranzyme 3の精製

    平田 幸代, 李 卿, 稲垣 弘文, 南 正康

    生化学   74 ( 8 )   1000 - 1000   2002.8

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  • 大腸菌によるヒトrecombinant Granzyme 3の発現

    平田 幸代, 李 卿, 稲垣 弘文, 南 正康

    生化学   73 ( 8 )   793 - 793   2001.8

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  • 有機リン農薬によるNK,LAK及びCTL活性低下の機序

    李 卿, 永原 則之, 平田 幸代, 南 正康

    産業衛生学雑誌   43 ( 臨増 )   483 - 483   2001.3

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  • ラットMercaptopyruvate sulfurtransferaseの反応機構(2) Chloropyruvateは異なる2つの経路で活性を阻害する

    永原 則之, 中川 淑郎, 平田 幸代, 南 正康

    生化学   72 ( 8 )   822 - 822   2000.8

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  • N,N-diethylanilineによる急性毒性と血液毒性

    平田 幸代, 李 卿, 朴 順愛, 南 正康

    産業衛生学雑誌   42 ( 臨増 )   350 - 350   2000.3

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  • 有機リン農薬によるNK細胞及び細胞傷害性T細胞活性への影響

    李 卿, 平田 幸代, 朴 順愛, 南 正康

    産業衛生学雑誌   42 ( 臨増 )   347 - 347   2000.3

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  • N,N-diethylanilineのマウスNK活性,CTL活性及びリンパ球幼若化反応に対する影響

    李 卿, 平田 幸代, 朴 順愛, 南 正康

    産業衛生学雑誌   41 ( 臨増 )   317 - 317   1999.4

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    DOI: 10.1539/sangyoeisei.KJ00001991076

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  • 血管内皮細胞のTFPI発現に対する酸化LDLの影響

    平田 幸代, 平石 さゆり, 堀江 修一, 風間 睦美

    日本薬学会年会要旨集   118年会 ( 3 )   81 - 81   1998.3

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Presentations

  • HuH-7細胞によるコリンエステラーゼの発現に対するオレイン酸の影響

    平田幸代, 稲垣弘文, 清水孝子, 李英姫, 川田智之

    薬学会第143年会  2023.3 

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  • HuH-7細胞によるコリンエステラーゼの産生に対するオレイン酸の影響

    平田幸代, 稲垣弘文, 清水孝子, 李英姫, 川田智之

    第95回日本生化学会大会  2022.11 

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  • HuH-7細胞の増殖によるコリンエステラーゼの産生量の変化

    平田幸代, 稲垣弘文, 清水孝子, 李英姫, 川田智之

    日本薬学会第142年会  2022.3 

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  • ヒト血清コリンエステラーゼに対するSandwich ELISAの改良

    平田幸代, 稲垣弘文, 清水孝子, 李英姫, 川田智之

    第94回 日本生化学会大会  2021.11 

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  • HuH-7細胞によるアセチルコリンエステラーゼ及びブチリルコリンエステラーゼの発現

    平田 幸代, 稲垣 弘文, 川田 智之

    日本薬学会 第141年会  2021.3 

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  • HuH-7細胞によるコリンエステラーゼの産生

    平田幸代, 五十嵐公一, 伊藤遼, 稲垣弘文, 川田智之

    薬学会第140年会  2020.3 

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Research Projects

  • 肝の脂肪化における血清コリンエステラーゼ活性上昇とその性状

    Grant number:20K10456  2020.4 - 2024.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    平田 幸代, 川田 智之, 稲垣 弘文, 李 英姫

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    ①血清ChEのSandwich ELISAの感度向上
    昨年度に確立したSandwich ELISAの感度をさらに向上させるために、現在のテトラメチルベンジジンによる発色ELISAをDELFIAへの変更を行った。DELFIAは、ランタニドキレート標識のストレプトアビジンと配位子を含むEnhancement solutionを反応させることで、強い蛍光を持つキレートのミセルを形成させた後、時間分解蛍光を測定する方法である。DELFIAで測定を行ったところ、感度は2倍程度しか向上できず、さらに値の再現性が低い結果となった。原因として、プレートの材質による影響が考えられた。
    ②HuH-7細胞の増殖に伴うChE量の変化
    HuH-7細胞を培養した時の培養上清中のChE量の変化について検討した。HuH-7細胞を2x10^4 cells/wellで4ウェルプレート(1.9 cm2)に播種し、1 mLのRPMI1640-10%FBS培地で20日間培養した。培養後、3、6、9、13、16、20日目に培養上清を回収し、細胞数をカウントした。培養上清中のChE及びアルブミンは、Sandwich ELISAで測定した。
    HuH-7細胞は、9日目まで増加し、以降はほぼ横ばいとなった(全日程で生存率は90%以上であった)。培養上清中のChEは9日目以降から検出され、13日目まで急激に濃度が上昇し、以降は緩やかに上昇した。一方アルブミンは、6日目以降から検出され、その後はほぼ一定の割合で増加し続けた。従ってChEは、HuH-7細胞が増殖している間はほとんど産生されず、増殖しなくなってから産生されると考えられた。すなわち、アルブミンよりもChEを測定することで、HuH-7細胞の状態をより鋭敏に捉えられる可能性が考えられた。

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  • Exacerbation effects and molecular mechanism of diesel exhaust particles in pulmonary fibrosis

    Grant number:18K10032  2018.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

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    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

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  • Role of Nrf2 in Neutrophilic Allergic Athsma

    Grant number:15K08786  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    LI YINGJI, SHIMIZU Takako

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    Grant amount:\4940000 ( Direct Cost: \3800000 、 Indirect Cost:\1140000 )

    In the present study, we investigated the role of Nrf2 on an experimental model of Ovalbumin (OVA) - sensitized and challenged allergic airway inflammation in both of BALB/c and C57BL/6 mice.
    Nrf2+/+ and Nrf2-/- mice were used in both of BALB/c and C57BL/6 mice. Allergic airway inflammation was generated in the mice by intraperitoneal sensitization with OVA/alum, and the mice were challenged with OVA intranasally. The several parameters such as inflammatory cytokines, IgE, and anti-oxidation index were examined in the bronchoalveolar lavage (BAL) fluid, serum, and lung tissues.
    In conclusion, the role of Nrf2 in the generation of allergic airway inflammation differs markedly between mouse strains. Our results suggest that Nrf2 may play a key role in the development of allergic airway inflammation related to neutrophils in Th2 type BALB/c mice.

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  • Molecular mechanisms of exacerbation effects on mouse lung fibrosis induced by diesel exhaust particles

    Grant number:24590764  2012.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    LI YINGJI, KAWADA Tomoyuki, AZUMA Arata, INAGAKI Hirofumi, HIRATA Yukiyo

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    Grant amount:\5330000 ( Direct Cost: \4100000 、 Indirect Cost:\1230000 )

    The accumulation of fibroblasts plays a critical role in the development of pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) process is related with pulmonary fibrosis progression. The current study was designed to explore the role of Diesel exhaust particle (DEP) whether or not induce EMT process in airway epithelial cells by oxidative stress. In the bronchial epithelial cell line, E-cadherin expression was down-regulated and N-cadherin expression was up-regulated by DEP exposure. The EMT cells migration was significantly increased and the antioxidant enzymes mRNA expression was up-regulated by DEP. These changes by DEP exposure were blocked by N-acetylcysteine pretreatment. Our results suggest that DEP may exacerbate the tissue remodeling processes of pulmonary fibrosis by oxidative stress.

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  • A study on stress evaluation of the second hand smoke exposure by salivary catecholamine metabolites

    Grant number:21500663  2009 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    KATSUMATA Masao, KAWADA Tomoyuki, INAGAKI Hirofumi, HIRATA Yukiyo, HIRATA Kimiko

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    The purpose of this study was to perform stress evaluation of the second hand smoke (SHS) exposure by salivary catecholamine metabolites. SHS exposure was surveyed by a questionnaire, and salivary cotinine level was measured for the nonsmokers. Then, the subjects were loaded with Uchida-Kraepelin test, and salivary cortisol and 3-Methoxy-4-hydroxyphenylglycol (MHPG) of catecholamine metabolite level was measured. Salivary MHPG level of a subject exposed to second hand smoke was significantly high after Uchida-Kraepelin test. Therefore, the salivary MHPG level was suggested to be valuable as a stress evaluation of second hand smoke exposure.

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  • Can human plasma granzyme 3 be used as a biological marker for inflammation?

    Grant number:21590669  2009 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    INAGAKI Hirofumi, HIRATA Yukiyo, KAWADA Tomoyuki, OTSUKA Toshiaki

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    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

    A new sandwich ELISA for human granzyme 3 was established using monoclonal antibodies raised against recombinant human granzyme 3 produced in E. coli. On the other hand, human peripheral blood lymphocytes were shown to secrete enzymatically inactive precursor of granzyme 3 (progranzyme 3) to the culture medium in vitro. Therefore, new monoclonal antibodies against progranzyme 3 were prepared. Using these antibodies, we could measure active granzyme 3 and inactive progranzyme 3 separately. Granzyme 3 concentrations in human plasma samples from healthy donors were very low and less than the detection limit of the ELISA.

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  • Research on the contribution to mouse pulmonary fibrosis of the oxidative stress induced by diesel exhaust particles

    Grant number:21590668  2009 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    LI Yingji, KAWADA Tomoyuki, AZUMA Arata, INAGAKI Hirofumi, HIRATA Yukiyo, SAOTOME Takako

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    Our results suggest that oxidative stress caused by diesel exhaust particles(DEPs) might be an important risk factor on the bleomycin(BLM) induced lung fibrosis, and the preventive effect by antioxidant is expected.

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  • New mechanism of organophosphorus pesticide-induced immunotoxocity : organophosphorus pesticide-induced apoptosis in immune cells

    Grant number:19590602  2007 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    LI QING, KAWADA Tomoyuki, INAGAKI Hirofumi, HIRATA Yukiyo, SATO Shigeru

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    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    We previously found that organophosphorus pesticides (OPs) significantly inhibited natural killer (NK) activity, which is mediated by the following mechanisms : 1) OPs impair the granule exocytosis pathway of NK, LAK and CTL cells by inhibiting the activity of granzymes (Li et al., 2002) and by decreasing the intracellular level of perforin, granzyme A, and granulysin, which was mediated by inducing degranulation of NK cells, and by inhibiting the transcription of mRNAs of perforin, granzyme A, and granulysin ; 2) OPs impair the FasL/Fas pathway of NK, LAK and CTL cells, as investigated by using perforin-knockout mice, in which the granule exocytosis pathway of NK cells does not function and only the FasL/Fas pathway remains functional. However, the above two mechanisms cannot completely explain the all mechanism of OP-induced inhibition of NK activity and there must be other mechanisms involve. This encourages us to speculate that OPs may induce apoptosis in NK and CTL and ultimately inhibited cytolytic activity of effectors.
    In order to explore the mechanism of OP pesticide-induced immunotoxicity, we investigated whether OP pesticides can induce apoptosis in human natural killer (NK) cells. NK-92CI and NK-92MI cells, which are interleukin-2 independent human NK cell lines, express CD56, perforin, granzymes A, B, 3/K, and granulysin and are highly cytotoxic to K562 cells in the chromium release assay were treated with DDVP or CP in vitro. It was found that DDVP and CP significantly induced apoptosis in NK-92 cells in a dose- and time-dependent manner. DDVP also induced an increase in intracellular active caspase-3 in NK-92CI cells in a dose- and time-dependent manner, and a caspase-3 inhibitor, Z-DEVD-FMK, significantly inhibited DDVP-induced apoptosis, suggesting that this apoptosis is partially mediated by the activation of intracellular caspase-3. The pattern of apoptosis induced by CP differed from that induced by DDVP. CP showed a faster response than DDVP at higher doses ; whereas, DDVP showed a slower but stronger apoptosis-inducing ability than CP at lower doses. Moreover, the response to OP pesticides differed between NK-92CI and NK-92MI cells, and NK-92CI cells were more sensitive to OP pesticides than NK-92MI cells. This is similar to the inhibition of NK activity induced by DDVP, in which NK-92CI cells were more easily inhibited by DDVP than NK-92MI cells and strongly suggested a relationship between DDVP-induced apoptosis and the inhibition of cytolytic activity in NK cells. Taken together, these findings suggest that OP pesticide-induced inhibition of NK activity may be at least partially mediated by OP pesticide-induced apoptosis in NK cells.
    To explore the mechanism of OP pesticide-induced inhibition of cytotoxic T lymphocyte (CTL) activity, it was also investigated whether OP pesticides can induce cell death/apoptosis in T cells using Jurkat human T cells in vitro. It was found that CP induced the cell death of Jurkat human T cells in a dose- and time-dependent manner. CP also induced apoptosis in Jurkat T cells in a dose- and time-dependent manner suggesting that CP-induced cell death consisted of apoptosis. CP also induced an increase in intracellular active caspase-3 in Jurkat T cells in a dose- and time-dependent manner, and Z-DEVD-FMK significantly inhibited CP-induced apoptosis. These findings indicate that CP can induce apoptosis in human Jurkat T cell cells, and this effect is partially mediated by the activation of intracellular caspase-3.
    To investigate the effect of OP on the splenocytes and the underlying mechanism in vivo, Fenitrothion (FNT) and its main metabolite, 3-methyl-4-nitrophenol (MNP) were administered orally to Wistar rats in daily doses of 0, 5 and 10mg/kg, 4-5 days/week for 9 weeks. Splenocytes were harvested from control and exposed rats, and the following cell phenotypes were quantified by flow cytometry : (1) B cells, (2) T cells, (3) T cell subsets (CD4/CD8), (4) natural killer (NK) cells, and (5) macrophages. Body weight, weight of the spleen and histopathological alterations of spleens were also examined. The percentage of splenic CD8+ T cells and the ratio of CD8/CD4 in the group receiving 10mg/kg FNT, and the percentages of splenic CD3+ and CD8+ T cells in the group receiving 10mg/kg MNP were significantly decreased compared with those in the controls. FNT exposure also significantly decreased the weight of the spleen and body weight. In addition, apoptotic lymphocytes in spleen were observed in FNT-exposed rats under transmission electron microscope. However, FNT and MNP exposures did not affect splenic NK cells, B cells, and macrophages. The above findings indicate that FNT and MNP may selectively affect splenic T cells in rats.

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