記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Epithelial-mesenchymal transition (EMT) is critical for embryonic development, and this process is recapitulated in adults during wound healing, tissue regeneration, fibrosis and cancer progression. Cell migration is believed to play a key role in both normal wound repair and in abnormal tissue remodeling. Prostaglandin E-2 (PGE(2)) inhibits fibroblast chemotaxis, but stimulates chemotaxis in airway epithelial cells. The current study was designed to explore the role of PGE(2) and its four receptors on airway epithelial cell migration following EMT using both the Boyden blindwell chamber chemotaxis assay and the wound closure assay. EMT in human bronchial epithelial cells (HBECs) was induced by TGF-beta(1) and a mixture of cytokines (IL-1 beta, TNF-alpha, and IFN-gamma). PGE(2) and selective agonists for all four EP receptors stimulated chemotaxis and wound closure in HBECs. Following EMT, the EP1 and EP3 agonists were without effect, while the EP2 and EP4 agonists inhibited chemotaxis as did PGE(2). The effects of the EP2 and EP4 receptors on HBEC and EMT cell migration were further confirmed by blocking the expected signaling pathways. Taken together, these results demonstrate that PGE(2) switches from a stimulator to an inhibitor of cell migration following EMT of airway epithelial cells and that this inhibition is mediated by an altered effect of EP2 and EP4 signaling and an apparent loss of the stimulatory effects of EP1 and EP3. Change in the PGE(2) modulation of chemotaxis may play a role in repair following injury. (C) 2014 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.prostaglandins.2014.10.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER PHYSIOLOGICAL SOC  

This study assessed the effect of extended exposure to cigarette smoke extract (CSE) on tissue repair functions in lung fibroblasts. Human fetal (HFL-1) and adult lung fibroblasts were exposed to CSE for 14 days. Senescence-associated beta-galactosidase (SA beta-gal) expression, cell proliferation, and tissue repair functions including chemotaxis and gel contraction were assessed. HFL-1 proliferation was inhibited by CSE and nearly half of the CSE-exposed cells were SA beta-gal positive after 14 days exposure, whereas 33% of adult lung fibroblasts were SA beta-gal positive in response to 10% CSE exposure. The SA beta-gal-positive cells did not proliferate as indicated by bromodeoxyuridine incorporation. In contrast, cells negative for SA beta-gal after CSE exposure proliferated faster than cells never exposed to CSE. These nonsenescent cells migrated more and contracted collagen gels more than control cells. CSE exposure stimulated TGF-beta(1) production, and both inhibition of TGF-beta receptor kinase and TGF-beta(1) siRNA blocked CSE modulation of fibroblast function. Extended exposure to CSE might induce two different fibroblast phenotypes, a senescent and a profibrotic phenotype. The fibroblasts that resist CSE-induced cellular senescence may contribute to the pathogenesis of idiopathic pulmonary fibrosis and could contribute to fibrotic lesions in chronic obstructive pulmonary disease acting through a TGF-beta(1)-mediated pathway. In contrast, the senescent cells may contribute to the pathogenesis of emphysema.

DOI： 10.1152/ajplung.00041.2014

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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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記述言語：日本語   出版者・発行元：(有)科学評論社  

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その他リンク： http://search.jamas.or.jp/link/ui/2013273074

記述言語：英語  

Epidemiological studies have shown that air pollutants, such as diesel exhaust particle (DEP), are implicated in the increased incidence of allergic airway disorders. In vitro studies of molecular mechanisms have focused on the role of reactive oxygen species generated directly and indirectly by the exposure to DEP. Antioxidants effectively reduce the allergic inflammatory effects induced by DEP both in vitro and in vivo. On the other hand, Nrf2 is a transcription factor essential for the inducible and/or constitutive expression of phase II and antioxidant enzymes. Disruption of Nrf2 enhances susceptibility to airway inflammatory responses and exacerbation of allergic inflammation induced by DEP in mice. Host responses to DEP are regulated by a balance between antioxidants and proinflammatory responses. Nrf2 may be an important protective factor against oxidative stresses induced by DEP in airway inflammation and allergic asthma and is expected to contribute to chemoprevention against DEP health effects in susceptible individuals. © 2013 Ying-Ji Li et al.

DOI： 10.1155/2013/323607

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER BASEL AG  

This study is designed to investigate the role of p38 MAPK in modulating human pulmonary artery endothelial cells (HPAECs) survival and tissue repair functions.
HPAECs (passage 8-12) were used for all experiments. Cells were treated with IL-1 beta (0.5 or 2 ng/ml) or p38 inhibitor (SB203580 or SB220025, 5 mu M each). Cells were also transfected with 50 nM siRNAs. Cell length was measured using ImageJ software. Collagen gel contraction and wound close assay were performed to evaluate tissue repair functions.
IL-1 beta activated p38 MAPK and induced morphologic change of HPAECs. The p38 inhibitors further augmented IL-1 beta-induced cell morphologic change, prevented cell death, and augmented collagen gel contraction. Suppression of p38 alpha, gamma, or delta, but not p38 beta resulted in cell morphologic alteration, and suppressing any one of p38 isoforms by siRNAs increased cell survival. Suppression of p38 alpha or delta augmented gel contraction. While p38 alpha suppression stimulated cell migration, suppressing the rest of three isoforms inhibit cell migration. Nuclear factor p65-siRNA blocked IL-1 beta-induced cell morphologic change, but did not affect p38 inhibitor-induced change.
These findings suggest that p38 MAPK may negatively modulate tissue repair functions of endothelial cells via p65 independent pathway.

DOI： 10.1007/s00011-011-0405-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER THORACIC SOC  

Fibroblasts are the major mesenchymal cells present within the interstitium of the lung and are a major source of vascular endothelial growth factor (VEGF), which modulates the maintenance of pulmonary microvasculature. Prostaglandin E-2 (PGE(2)) acts on a set of E-prostanoid (EP) receptors that activate multiple signal transduction pathways leading to downstream responses. We investigated the modulation by PGE(2) of VEGF release by human lung fibroblasts. Human lung fibroblasts were cultured until reaching 90% confluence in tissue culture plates, after which the culture media were changed to serum-free Dulbecco's modified Eagle's medium, with or without PGE(2), and with specific agonists or antagonists for each EP receptor. After 2 days, culture media were assayed for VEGF by ELISA. The results demonstrated that PGE(2) and the EP2 agonist ONO-AE1-259- 01 significantly stimulated the release of VEGF in a concentration-dependent manner. Agonists for other EP receptors did not stimulate the release of VEGF. The stimulatory effect of PGE(2) was blocked by the EP2 antagonist AH6809, but was not blocked by antagonists for other EP receptors. The protein kinase-A (PKA) inhibitor KT-5720 also blocked the stimulatory effect of PGE(2). The increased release of VEGF induced by PGE(2) was accompanied by a transient increase in the concentration of VEGF mRNA. These findings demonstrate that PGE(2) can modulate the release of VEGF by human lung fibroblasts through its actions in the EP2 receptor/PKA pathway. This activity may contribute to the maintenance of pulmonary microvasculature in the alveolar wall.

DOI： 10.1165/rcmb.2010-0115OC

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

Introduction. The relationship among lifestyle, aging and psychological wellbeing was evaluated in Japanese working men.
Methods. Self-administered questionnaire on six lifestyle factors and the General Health Questionnaire 12-item version (GHQ12) were administered to 3306 male workers. Health practice index (HPI) was calculated as a desirable lifestyle score by summing up each binary lifestyle score (0, 1), ranging from 0 to 6. To check validity of the study outcome, the authors repeated twice with 1 year interval. HPI was categorised into three groups by the score of 0-2, 3-4 and 5-6.
Results. The number of subjects categorised by HPI was 532, 1967 and 807, respectively. The mean value of GHQ12 significantly decreased as the HPI increased by adjusting age. Multiple regression analysis was conducted to predict GHQ12 by six lifestyle scores, and age, sleep, night snacking and exercise were significantly related to GHQ12. Multiple logistic regression analysis was conducted and age in 50s, two-shift work, sleep, night snacking and exercise were significantly associated with GHQ12.
Conclusion. Although cause-effect relationship cannot make clear, some of desirable health practices and aging were closely related to psychological wellbeing judged by GHQ12.

DOI： 10.3109/13685538.2010.493588

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOSBY-ELSEVIER  

Background: Fibroblast heterogeneity is recognized, and fibroblasts from diseased tissues, including those of asthmatic subjects, have functional phenotypes that differ from normal tissue. However, progenitor-progeny relationships and the factors that control fibroblast differentiation are poorly defined.
Objective: We sought to determine whether IL-4 could alter the functional phenotype of fibroblasts during their differentiation from stem/progenitor cells.
Methods: Using a 3-dimensional collagen gel system, we obtained embryoid bodies derived from human embryonic stem cells and recovered spindle-shaped cells consistent with fibroblasts that had differentiated in the presence or absence of IL-4.
Results: IL-4-induced fibroblast-like cells were more active in contraction of collagen gels, migration, and production of fibronectin than control (without IL-4) cells. IL-4-induced cells demonstrated less expression of miR-155, which modulated contraction, migration, and fibronectin production. These differences persisted in culture without further addition of IL-4, suggesting the differentiated phenotype might be a permanent alteration.
Conclusion: The current study demonstrates that IL-4 induces differentiation of stem/precursor cells into fibroblast-like cells that demonstrate a more fibrogenic phenotype, which is due to reduced expression of miR-155. These findings provide a novel mechanism for the persistent abnormalities in IL-4-related diseases and a novel target to regulate tissue remodeling by fibroblasts. (J Allergy Clin Immunol 2011;127:1595-603.)

DOI： 10.1016/j.jaci.2011.01.049

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aims: There is an ethnic difference of obesity index to diagnose metabolic syndrome. The authors explored the optimal cut-off levels for body mass index (BMI) and waist circumference (WC) in relation to each component of metabolic syndrome. Materials and methods: Receiver operating characteristics (ROC) analysis was used to determine the optimal cut-off levels for each component of metabolic syndrome. This study included 4572 workers aged 42.5 ± 9.9 years. Results: The optimal BMI cut-off values for diabetes mellitus, hypertension or dyslipidemia varied from 23.0 to 24.3 kg/m2. As for WC, the optimal cut-off values varied from 83.0 to 83.7 cm. The optimal BMI cut-off values relating with one to three components of metabolic syndrome varied from 23.2 to 25.3 kg/m2. As for WC, the optimal cut-off values varied from 83.0 to 85.0 cm. Pair-wise comparison of ROC curves showed that WC has an advantage in relation to metabolic syndrome and its components compared with BMI. By logistic regression analysis, odds ratios of obesity indices for hypertension, dyslipidemia or the number of metabolic component were all significantly increased. As for diabetes mellitus, odds ratios of BMI ≥25 and WC ≥85 significantly increased, respectively. Conclusions: Japanese criteria of obesity in metabolic syndrome in man may be appropriate for diabetes mellitus. Ethnic difference in criteria of obesity in Asian metabolic syndrome exists, and mutual comparisons in the prevalence of metabolic syndrome have a difficulty to conduct. © 2010 Diabetes India. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.dsx.2010.05.012

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1165/rcmb.2009-0163OC

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DOI： 10.2147/JIR.S19461

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IOS PRESS  

Objective: It has been suggested that the presence of a depressive state is a predictor of increase of the body weight. However, to precisely understand the nature of this relationship, the data should be controlled for other factors that can also be associated with weight gain.
Methods and Participants: To test the hypothesis that the presence of a depressive state is associated with future weight gain, a 4-year prospective occupation-based cohort study was conducted in male adult workers (N = 1730) at a railway company. Following the initial screening, follow-up information was obtained via a legally required annual health examination. The presence of a depressive state was identified using the Zung Self-Rating Depression Scale (SDS). The weight of each participant was measured to the nearest kilogram. Multiple logistic regression analysis was used to test the association between the depressive state and a weight gain of 4 kg or more over the 4-year study period after controlling for potentially confounding variables such as the age, smoking status, alcohol intake status, and physical activity.
Results: A weight gain of 4 kg or more over the 4-year study period was significantly associated with the depressive state, even after controlling for confounding variables (p < 0.05). Short-term longitudinal analysis also revealed an association between the depressive state and subsequent increase of the body weight.
Conclusion: Since the depressive state was demonstrated to be an important risk factor for increase of the body weight, further research on depression should be conducted with a view to providing effective health education.

DOI： 10.3233/WOR-2011-1114

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier Ltd  

Background: The aim of this study was to examine the association between serum insulin levels and components of the metabolic syndrome (MetS) in working women. Methods: The target subjects were 141 working women. Serum triglyceride, HDL cholesterol, uric acid, plasma insulin and plasma glucose were measured in addition to waist circumference and blood pressure. Results: MetS was diagnosed based on the modified criteria of the International Diabetes Federation, and was present in 7.1% (10/141) of the study subjects. Stepwise multiple regression analysis showed that some components of MetS were significantly associated with log-transformed values of the serum insulin. The standardized regression coefficient for the waist circumference, high density lipoprotein cholesterol, systolic blood pressure and age were 0.238, -0.333, 0.309 and -0.156, respectively. Conclusions: A statistically significant relationship existed between the components of MetS and the serum insulin levels in working women. © 2010 Diabetes India.

DOI： 10.1016/j.dsx.2010.12.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

We have recently reported that disruption of nuclear erythroid 2 P45-related factor 2 (Nrf2) enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles (DEP) in mice. C57BL/6 Nrf2 knockout (Nrf2(-/-)) mice and wild-type (Nrf2(+/+)) mice were further exposed to low-dose DEP for 7 h/day, 5 days/week, for a maximum of 8 weeks. After exposure to DEP for 5 weeks, allergic airway inflammation was generated in the mice by intraperitoneal sensitization with OVA followed by intranasal challenge. Nrf2(-/-) mice exposed to relatively low-dose DEP showed significantly increased percentage changes relative to the OVA alone group in terms of airway hyperresponsiveness (AHR) and inflammatory cells, levels of IL-5 and thymus and activation regulated chemokine (TARC) in bronchoalveolar lavage (BAL) fluid than did Nrf2(+/+) mice. Lung tissues of Nrf2(-/-) mice after DEP exposure showed inflammatory cell infiltrates, and increased PAS staining-positive mucus cell hyperplasia. In contrast, the percentage changes relative to the OVA group in the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio in whole blood was higher in Nrf2(+/+) mice than in Nrf2(-/-) mice. By using Nrf2(-/-) mice, it was shown for the first time that relatively low-dose DEP exposure induces oxidant stress, and that host anti-oxidant responses play a key role in the development of DEP-induced exacerbation of allergic airway inflammation. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.clim.2010.07.014

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER THORACIC SOC  

Rationale: Persistent inflammation plays a major role in chronic obstructive pulmonary disease (COPD) pathogenesis, but its mechanisms are incompletely defined. Overproduction of the inflammatory mediator prostaglandin (PG) E-2 by COPD fibroblasts contributes to reduced repair function.
Objectives: The present study determined if fibroblasts from subjects with COPD overproduce PGE(2) after stimulation with the inflammatory cytokines IL-1 beta and tumor necrosis factor-alpha, and further defined the mechanism for overproduction.
Methods: Fibroblasts were isolated from parenchymal tissue obtained from smokers with and without COPD undergoing lung surgery. PGE(2), cyclooxygenases (COX), and miR-146a in these cells were evaluated by in vitro studies.
Measurements and Main Results: After stimulation with inflammatory cytokines, COPD fibroblasts produced 2.7-fold more PGE(2) compared with controls with similar smoking history. The increase in PGE(2) depended on induction of COX-2, which increased to a greater degree in fibroblasts from subjects with COPD. Cytokines also induced microRNA miR-146a expression in both fibroblasts, but significantly less in COPD fibroblasts. miR-146a caused degradation of COX-2 mRNA; reduced expression prolonged COX-2 mRNA half-life in fibroblasts from subjects with COPD. Cytokine-stimulated PGE(2) production and miR-146a expression in cultured fibroblasts correlated with clinical severity assessed by expiratory airflow and diffusion capacity.
Conclusions: miR-146a seems to play a pathogenetic role in the abnormal inflammatory response in COPD. Increased half-life of inflammatory mRNAs is a mechanism of abnormal inflammation in this disease.

DOI： 10.1164/rccm.201001-0055OC

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aims: The prevalence of glucose intolerance in the Japanese adult population is increasing. In this study, the associated factors including lifestyles with glucose intolerance and its metabolism were explored. Methods: A cross-sectional study was conducted in 2008. The sample included 3203 working men aged 35-59 years. Age, six lifestyle-related factors, and metabolic components were used as variables to calculate the odds ratio for glucose intolerance, which were defined if his fasting plasma glucose was ≥110 mg/dL and &lt
126 mg/dL. Results: The prevalence of glucose intolerance was 8.4%, and it increased with 5-year interval of age (2.2, 5.0, 10.4, 15.2, and 17.5%, respectively). Odds ratios (95% confidence interval) of age, obesity, hypertension, dyslipidemia, and no current smoking for glucose intolerance were 1.11 (1.09-1.13), 1.66 (1.31-2.11), 1.90 (1.47-2.47), 1.86 (1.46-2.36), and 0.79 (0.62-0.998), respectively. In contrast, the odds ratios of drinking, sleeping, exercise, and dietary habit did not reach the significance level, although multiple regression analysis presented that subjects with regular exercise showed significantly lower serum insulin level. Conclusions: The risk of glucose intolerance was significantly correlated with obesity, high blood pressure, dyslipidemia and smoking habit. However, other lifestyle factors were not significantly associated with glucose intolerance. © 2010 Diabetes India. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.dsx.2010.05.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

Introduction. Statistical information regarding the prevalence of metabolic syndrome among a wide age range of workers is insufficient.
Methods. A total of 4278 men between the ages of 20 and 59 years participated in the study. Metabolic syndrome was diagnosed according to the International Diabetes Federation (IDF) and the National Cholesterol Education Program (NCEP) III criteria.
Results. Overall, the prevalences of metabolic syndrome according to the IDF and NCEPIII criteria were 13.6% and 14.8%, respectively. The prevalence of metabolic syndrome according to the IDF (NCEPIII) criteria among workers in their 20s, 30s, 40s, and 50s were 4.8% (6.1%), 9.9% (12.2%), 18.4% (21.6%) and 25.8% (34.0%), respectively. A plot of the prevalence of metabolic syndrome according to the NCEPIII criteria versus age had a steep gradient and increased sharply for men in their 50s. In contrast, a plot of the prevalence of metabolic syndrome according to the IDF criteria versus age increased in a linear manner.
Conclusion. The prevalence of metabolic syndrome increased among workers according to age, but the increasing trend and the absolute prevalence of metabolic syndrome differed according to the two sets of diagnostic criteria used in this study.

DOI： 10.3109/13685531003586983

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

Introduction. Shift work has been reported to be associated with an increase in the metabolic syndrome (MetS). To clarify the association between the type of shift work and the risk of MetS, a cross-sectional field survey was conducted after adjusting for age and lifestyle factors.
Methods. The subjects were 3007 Japanese males, aged 34-64 years old, who were employees (1700 day and 1307 shift workers) of a car-manufacturing company. The standard Japanese criteria for the diagnosis of MetS was used. Age, smoking habit, drinking habit, sleeping habit and exercise habit were used as the independent variables.
Results. The prevalence of MetS in the day workers, two-shift workers, and three-shift workers were 13.8% (234/1700), 10.7% (120/1125) and 17.6% (32/182), respectively. There was a significant difference in the prevalence between the two-shift workers and the day workers. Estimation of the odds ratios (95% confidence intervals) of age, two-shift work and habitual exercise for MetS were 1.03 (1.01-1.04), 0.77 (0.61-0.98) and 0.64 (0.51-0.81), respectively.
Conclusion. Two-shift work was associated with lower risk of MetS, which is not in accordance with past reports. This finding should therefore be re-analysed, including investigation of the job content in each group.

DOI： 10.3109/13685530903536692

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Serum uric acid and hematological parameters play a significant role for cardiovascular disease (CVD). The metabolic syndrome (MetS) is associated with CVD, but the relationship between such blood parameters and MetS has not yet been precisely investigated in healthy workers. Methods: A total of 1088 male workers in a pharmaceutical company, aged 30-59 years with mean age of 43.2, were recruited. They participated in annual health examination in 2009. MetS was diagnosed according to the NCEP-ATP III criteria with modification on waist circumference. The relationships between blood parameters and MetS were analyzed according to four groups stratified by the number of components on MetS (0, 1, 2 and 3-5) in combination with age. Results: There was a significant trend of increase of variables such as hematocrit, white blood cell count (WBC), platelet count and serum uric acid as the number of components on MetS increased (p &lt
0.05). Among them, there was a significant difference in the mean value except platelet count between a group of MetS and other groups. Furthermore, serum uric acid, WBC count and age were significantly associated with MetS by logistic regression analysis. Odds ratios and 95% confidence intervals in parentheses of uric acid and WBC against MetS were 1.47 (1.28-1.69) and 1.34 (1.21-1.49), respectively. Conclusions: Serum uric acid and WBC were associated with MetS, and such blood parameters increased as the number of MetS components increased in Japanese male workers. © 2010 Diabetes India. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.dsx.2010.05.016

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Objective: We performed a 1-year follow-up study to determine the effects of smoking status and insulin resistance on the prevalence of metabolic syndrome.
Methods: This study included 2136 workers without metabolic syndrome at baseline who were followed for 1 year. The subjects were divided into four categories of smoking and work history, respectively. Insulin resistance was evaluated using the homeostasis model assessment for insulin resistance (HOMA-R).
Results: The prevalence of metabolic syndrome after 1 year was 6.3%. A multiple logistic regression analysis showed that the current smokers category versus the nonsmokers category, a 0.1-point increase in the HOMA-R score, a 1-point increase in the uric acid level, age, and body mass index were significantly correlated with increased odds for metabolic syndrome, yielding odds ratios (95% confidence intervals) of 1.61 (1.09-2.39), 1.14 (1.04-1.25), 1.31 (1.12-1.54), and 1.06 (1.03-1.09), and 1.23 (1.15-1.31), respectively.
Conclusions: Current smoking, insulin resistance, uric acid level, and age contributed positively to the prevalence of metabolic syndrome. In contrast, smoking cessation within 1 year and work history did not contribute to metabolic syndrome. (C) 2009 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.orcp.2009.12.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Objective: This study was intended to identify significant determinant factors of insulin resistance.
Methods: Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-R) and was calculated as "Fasting plasma glucose x Fasting serum insulin)/405". The target subjects were 3008 working men. The serum lipid profiles, uric acid level, insulin level, plasma glucose level, hemoglobin A1C level, and blood pressure, in addition to the waist circumference or body mass index, were also measured. A stepwise multiple regression analysis was performed using log-transformed values of HOMA-R as the dependent variable.
Results: The standardized regression coefficient for waist circumference was about six times larger than that for hemoglobin A1c (0.45 and 0.08, respectively). The standardized regression coefficients for the other factors were 0.15 for diastolic blood pressure, 0.10 for the low-density lipoprotein cholesterol level, -0.06 for age, -0.04 for habitual exercise, 0.14 for no habitual drinking, and 0.07 for no smoking. When body mass index was substituted for waist circumference, almost the same results were obtained. The adverse effects of no smoking and no habitual drinking on the HOMA-R score might be explained, at least in part, by the relation of these factors with obesity. Regular exercise had a protective effect on lowering insulin resistance.
Conclusions: A close relation exists between obesity-related indices (waist circumference and body mass index) and insulin resistance, independent of age and other vascular risk factors in Japanese working men. (C) 2009 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.orcp.2009.07.001

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記述言語：英語  

DOI： 10.1164/rccm.201001-0055OC

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Bentham Science Publishers B.V.  

Epidemiological studies have shown that particulate air pollutants, such as diesel exhaust particles (DEPs) are implicated in the increased incidence of allergic airway disorders. DEPs induce and exaggerate allergic airway inflammation in vitro and in vivo. Studies of molecular mechanisms have focused on the role of reactive oxygen species (ROS) generated directly and indirectly by exposure to DEPs. The ROS play an important role in proinflammatory reaction in airways. Nuclear erythroid 2 P45-related factor 2 (Nrf2) is a key transcription factor that regulates host antioxidant and contributes to regulate airway inflammation and exacerbation of allergic inflammation induced by DEPs. The authors demonstrated that DEPs-induced oxidants stress and resultant inflammatory changes were blocked by antioxidants such as N-acetyl cysteine (NAC). Therefore, chemoprevention against DEPs health effects in susceptible individuals may become a choice for future environmental protection policy. © 2010 Bentham Science Publishers Ltd.

DOI： 10.2174/187152810793358787

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

We have recently reported that airway inflammatory responses to the oxidative stress induced by prolonged low-dose diesel exhaust particle (DEP) exposure differ markedly between BALB/c and C57BL/6 mice. In the present study, the effects of genetic differences in the response to prolonged low-dose DEP exposure on the generation of ovalbumin-induced allergic airway inflammation were further explored using the same mouse strains. In BALB/c mice, eosinophils and mucous goblet cells in histopathological pulmonary specimens increased significantly after DEP exposure, and were more marked than in C57BL/6 mice. Interleukin (IL)-5 and IL-13 levels in bronchoalveolar lavage (BAL) fluid were increased significantly by DEP exposure only in BALB/c mice. The DEP-induced increases in peribronchial eosinophils and mucous goblet cells in the lung tissues, and of IL-5 and IL-13 in the BAL fluid, were significantly attenuated by the antioxidant N-acetylcysteine. Thus, the effects of prolonged low-dose DEP exposure on the generation of allergic airway inflammation differed markedly between the mouse strains. These differences may be caused by different antioxidant responses to the oxidative stress induced by DEP exposure. Our results contribute more information to the search for genetic susceptibility factors in the response to DEP, and may thus assist in the discovery of new biomarkers for DEP-related disease.

DOI： 10.1080/08923970802383316

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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 >= 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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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

MicroRNA plays an important role in cell differentiation, proliferation and cell death. The current study found that miRNA-146a was up-regulated in human bronchial epithelial cells (HBECs) in response to stimulation by TGF-beta 1 Plus cytomix (a mixture of IL-1 beta, IFN-gamma and TNF-alpha). TGF-beta 1 plus cytomix (TCM) induced apoptosis in HBECs (3.4 +/- 0.6% of control vs 83.1 +/- 4.0% of TCM treated cells, p < 0.01), and this was significantly blocked by the miRNA-146a mimic (8.8 +/- 1.5%, p < 0.01). In contrast, a miRNA-146a, inhibitor had only a modest effect on cell survival but appeared to augment the induction of epithelial-mesenchymal transition (EMT) in response to the cytokines. The MicroRNA-146a mimic appears to modulate HBEC survival through a mechanism of up-regulating Bcl-XL and STAT3 phosphorylation, and by this mechanism it could contribute to tissue repair and remodeling. (C) 2009 Elsevier Inc. All rights reserved

DOI： 10.1016/j.bbrc.2009.01.066

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

To test our hypothesis that diesel exhaust particle (DEP)-induced oxidative stress and host antioxidant responses play a key role in the development of DEP-induced airway inflammatory diseases, C57BL/6 nuclear erythroid 2 P45-related factor 2 (Nrf2) knockout (Nrf2(-/-)) and wild-type mice were exposed to low-dose DEP for 7 h/day, 5 days/week, for 8 weeks. Nrf2(-/-) mice exposed to low-dose DEP showed significantly increased airway hyperresponsiveness and counts of lymphocytes and eosinophils, together with increased concentrations of IL-12 and IL-13, and thymus and activation-regulated chemokine (TARC), in BAL fluid than witd-type mice. In contrast, expression of antioxidant enzyme genes was significantly higher in wild-type mice than in Nrf2(-/-) mice. We have first demonstrated that disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by inhalation of tow-dose DEP in mice. These results strongly suggest that DEP-induced oxidative stress and host antioxidant responses play some role in the development of DEP-induced airway inflammation. (C) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.clim.2008.05.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Clinical studies have demonstrated that gefitinib, an epidermal growth factor receptor inhibitor, is an effective treatment for some patients with advanced non-small cell lung cancer and is generally well-tolerated. However, several reports have also suggested that gefitinib is associated with acute lung injury and subsequent fibrosis. One hypothesis is that gefitinib exacerbates lung injury induced by radiation therapy. It is important to confirm the safety of gefitinib in radiotherapy for patients with lung cancer. In this preclinical study we aimed to clarify the effect of gefitinib on thoracic radiotherapy. Six-week-old female C57BL/6 mice were immobilized in a plastic frame, and the thorax was irradiated once with a dose of 12 Gy on day 0. Gefitinib (20, 90 and 200 mg/kg/day) was administered on days 0 to 5 (acute phase) or days 14 to 19 (late phase) postirradiation. Thoracic irradiation induced lung injury and subsequent fibrosis 5 months later. Gefitinib, administered in the acute phase, had no effect on lung fibrosis or collagen levels induced by irradiation. A high dose of gefitinib (200 mg/kg/day) administered during the late phase significantly reduced fibrosis scores and collagen levels. These results suggest that gefitinib does not exacerbate radiation-induced lung injury and fibrosis in this strain of mice. Therefore, thoracic irradiation is unlikely to be a risk factor for lung injury associated with gefitinib treatment.

DOI： 10.1272/jnms.75.96

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

The authors used BALB/c and C57BL/6 mouse strains to search for genetically based differences in response to prolonged (6 months) low-dose (100 mu g/m(3)) diesel exhaust particle (DEP) exposure from birth in terms of airway inflammatory responses. Histopathological assessment showed that inflammatory cells infiltrated the perivascular areas only in C57BL/6 mice. The count of DEP-laden alveolar macrophages in bronchoalveolar lavage (BAL) fluid was significantly greater in BALB/c mice (P < .05) than in C57BL/6 mice. The lymphocyte and eosinophil count in BAL fluid was significantly greater in C57BL/6 mice (P < .05) than in BALB/c mice. Immunoglobulin (Ig) IgG(1) and IgG(2) levels in serum, and the monocyte chemoattractant protein (MCP)-1 level in BAL fluid were significantly greater in BALB/c mice than in C57BL/6 mice. The interleukin (IL)-12 level in BAL fluid was significantly greater in C57BL/6 mice than in BALB/c mice, but the IL-13 level in BAL fluid was significantly less in BALB/c mice than in C57BL/6 mice. Glutathione S-transferase (GST) mRNA expression and protein production in lung tissues were significantly lower in C57BL/6 mice than in BALB/c mice, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in the lung tissues were significantly greater in C57BL/6 mice than in BALB/c mice. In conclusion, prolonged low-dose DEP exposure induces airway inflammatory responses that differ remarkably among mouse strains; these differences are caused by differences in the host defense response to the oxidative stress induced by DEP exposure and may be useful in the development of biomarkers.

DOI： 10.1080/01902140701884406

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WICHTIG EDITORE  

anti-We previously reported that forest bathing trips enhanced human NK activity, number of NK cells, and intracellular anti-cancer proteins in lymphocytes, and that the increased NK activity lasted for more than 7 days after the trip in male subjects. In the present study, we investigated the effect of forest bathing trip on human NK activity in female subjects. Thirteen healthy nurses, age 25-43 years, professional career 4-18 years, were selected with informed consent. The subjects experienced a three-day/two-night trip to forest fields. On day 1, the subjects walked for two hours in the afternoon in a forest field; on day 2, they walked for two hours each in the morning and afternoon in two different forest fields; and on day 3, the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire. Blood and urine were sampled on the second and third days during the trip, and on days 7 and 30 after the trip. NK activity, numbers of NK and T cells, and granulysin, perforin, and granzymes A/B-expressing lymphocytes in the,blood samples, the concentrations of estradiol and progesterone in serum, and the concentrations of adrenaline and noradrenaline in urine were measured. Similar control measurements were made before the trip on a normal working day. The concentrations of phytoncides in the forests were measured. The forest bathing trip significantly increased NK activity and the numbers of NK, perforin, granulysin, and granzymes A/B-expressing cells and significantly decreased the percentage of T cells, and the concentrations of adrenaline and noradrenaline in urine. The increased NK activity lasted for more than 7 days after the trip. Phytoncides, such as alpha-pinene and beta-pinene were detected in forest air. These findings indicate that a forest bathing trip also increased NK activity, number of NK cells, and levels of intracellular anti-cancer proteins in female subjects, and that this effect lasted 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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/01902140802093238

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Low-dose diesel exhaust particle (DEP) exposure induces airway inflammation and exaggerates asthmatic responses in mice, but it is unclear whether strains differ in their susceptibility to adverse effects from low-dose DEP exposure. The authors used BALB/c and C57BL/6 mouse strains to search for genetically based differences in response to low-dose DEP (100 mu g/m(3)) exposure in terms of airway inflammatory response. The macrophage count in bronchoalveolar lavage (BAL) fluid soon after DE exposure began was significantly greater in C57BL/6 mice (P < .05) than that in BALB/c mice. The count did not increase significantly in BALB/c mice, until later. Heme oxygenase-1 (HO-1) mRNA expression and protein production in lung tissues soon after exposure began were more marked in BALB/c mice than in C57BL/6 mice, but the reverse was true later on. The increases in interleukin (IL)-1 beta and interferon (IFN)-gamma levels in BAL fluid after DE exposure were significant only in BALB/c mice; there were significantly increases in monocyte chemoattractant protein (MCP)-1, IL-12, IL-10, IL-4, and IL-13 in both strains, but these were more marked in C57BL/6 mice. These interstrain differences in airway inflammatory response after DE exposure were significantly attenuated by antioxidant N-acetylrysteine (NAC) treatment. Changes in airway hyperresponsiveness were independent of the airway inflammation induced by low-dose DEP. Thus, in BALB/c mice, innate immunity may play a central role in DE exposure response, whereas in C57BL/6mice Th2-dominant responses play a central role. Low-dose DEP exposure induces airway inflammatory responses that differ among strains, and these differences may be caused by differences in sensitivity to oxidative stress.

DOI： 10.1080/01902140701481062

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

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-beta). The expression of Smad3 and Smad4 mRNA in murine lung fibroblasts disappeared due to TGF-beta, but was recovered by EM703. EM703 inhibited the expression of p-Smad2/3 and Smad4 protein in murine lung fibroblasts induced by TGF-beta.
Conclusion: These findings suggest that EM703 improves bleomycin-induced pulmonary fibrosis in mice by actions of anti-inflammation and regulation of TGF-beta signaling in lung fibroblasts.

DOI： 10.1186/1465-9921-7-16

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER THORACIC SOC  

Pulmonary fibrosis is the result of abnormal processes of repair that occur after lung injury. Transforming growth factor (TGF)-beta is a key molecule in the progression of pulmonary fibrosis. Although clinical use of interferon (IFN)-beta did not improve survival in patients with idiopathic pulmonary fibrosis, because some preclinical studies have suggested that IFN-beta is a potent inhibitor of fibrogenesis, beneficial effects of IFN-beta have been expected. We therefore attempted to determine effects of IFN-beta and investigated the mechanism of action of IFN-beta in bleomycin-induced pulmonary fibrosis. Bleomycin at Day 0 and IFN-beta for 4 wk were administered intravenously to ICR mice. At 28 d after bleomycin injection, histologic and chemical analysis was performed for evaluation of effects of IFN-beta. Tissue distribution and amounts of TGF-beta1 and thrombospondin (TSP)-1/2 were analyzed. IFN-beta attenuated prolylhydroxylase activity, resulting in inhibition of pulmonary fibrosis. Bleomycin-induced increase in TGF-beta1 in epithelial cells and extracellular matrix was attenuated by IFN-beta. TSP-1/2 was limited in platelets of control mice, but was present in foamy cells in fibrotic regions induced by bleomycin. These findings suggest that the antifibrotic effect of IFN-beta is inhibition of TGF-beta and its activation via decrease in TSP-1/2 in lung tissue and change in location of TSP-1/2 from platelets to foamy cells.

DOI： 10.1165/rcmb.2003-0374OC

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER COLL CHEST PHYSICIANS  

Background and objective: Although the pathogenesis of interstitial pneumonia and pulmonary fibrosis are not well understood, it has been reported that inflammatory cells, especially neutrophils, and the injurious substances produced by them play important roles in the progression of interstitial pneumonia and subsequent fibrosis. Erythromycin and other 14-membered ring macrolides (14-MRMLs) have been reported to improve the survival of patients with diffuse panbronchiolitis by antineutrophil and several other anti-inflammatory mechanisms. The present study was undertaken to investigate the effects of 14-MRMLs on an experimental model of bleomycin-induced acute lung injury and subsequent fibrosis in mice.
Methods: Bleomycin was administered IV to ICR mice. At 28 days after bleomycin injection, fibrotic foci were histologically observed in left lung tissues, and hydroxyproline content in right lung tissues was chemically analyzed. The inhibitory effects of 14-MRMLs were assessed by overall comparison between control (normal saline solution [NS] alone), untreated (bleomycin alone), and treated (bleomycin plus 14-MRMLs) groups. For evaluation of early-phase inflammation, cell populations in BAL fluid and induction of messenger RNA (mRNA) of adhesion molecules (E-selectin, P-selectin, intercellular adhesion molecule I [ICAM-1], and vascular cell adhesion molecule 1 [VCAM-1]) in lung tissues were examined at 0 to 13 days after bleomycin treatment. These parameters were also compared with those for the control (NS alone), 14-MRML untreated (bleomycin alone), and 14-MRML pretreated (bleomycin plus 14-MRML pretreated) groups.
Results: Bleomycin-induced pulmonary fibrosis was inhibited by erythromycin and other 14-MRMLs on day 28 after bleomycin injection in ICR mice, especially those pretreated with 14-MRMLs. Hydroxyproline content in lung tissues was also decreased in the 14-MRML-pretreated groups. The number of neutrophils in BAL fluid significantly increased, with two peaks at I day and 9 days (from 6 to 11 days) after bleomycin administration. 14-MRMLs significantly inhibited both peaks of neutrophil infiltration into the airspace. Changes in mRNA expression of adhesion molecules (E-selectin, P-selectin, ICAM-1, VCAM-1) were associated with leukocyte migration into the airspace. 14-MRMLs clearly inhibited the induction of VCAM-1 mRNA, and tended to attenuate that of ICAM-1 mRNA, but inhibited the induction of neither E-selectin mRNA nor P-selectin mRNA.
Conclusion: These findings indicate that attenuation of inflammatory cell migration into the airspace by 14-MRMLs, especially of neutrophils and macrophages, resulted in inhibition of lung injury and subsequent fibrosis. 14-MRMLs clearly attenuated the expression of VCAM-I mRNA during the early phase of bleomycin-induced lung injury, and this might be one mechanism of inhibition of neutrophil and macrophage migration into the airspace by 14-MRMLs. This may be one mechanism of the anti-inflammatory and antifibrotic effects of 14-MRMLs. These findings suggest that prophylactic administration of 14-MRMLs may be clinically efficacious in preventing acute exacerbation of interstitial pneumonia and acute lung injury.

DOI： 10.1378/chest.122.6.2137

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Background: Although the pathogeneses of interstitial pneumonia are not well understood, it has been reported that inflammatory cells, especially neutrophils, and their injurious substances play important roles in the progression of interstitial pneumonia. Erythromycin and other 14-membered ring macrolides (14-MRMLs) have been reported to inhibit chronic airway inflammation by mechanisms of anti-neutrophil and several other anti-inflammatory activities. The present study was undertaken to investigate the effects and mechanisms of 14-MRMLs (erythromycin: EM
clarithromycin: CAM
roxithromycin: RXM) on an experimental model of bleomycin (BLM)-induced acute lung injury in mice. Methods: BLM was administered intravenously to ICR mice. For the evaluation of early-phase inflammation, cell populations in broncho-alveolar lavage fluid (BALF) and induction of mRNA of adhesion molecules (E-selectin, P-selectin, ICAM-1, VCAM-1) and TNF-α tested by RT-PCR in lung tissues were examined at 0 to 13 days after BLM. These parameters were also compared with those of the control (NS alone), 14-MRMLs-untreated (BLM alone) and- pre-treated (BLM+pre 14-MRMLs) groups. Results: The number of neutrophils, macrophages, and lymphocytes significantly increased in BAL. Neutrophils especially increased with two peaks after BLM administration. 14-MRMLs significantly inhibited both peaks of neutrophil. The increase in number of macrophages in BALF was significantly attenuated by EM and RXM, and slightly attenuated by CAM. Number of lymphocytes in BALF was significantly attenuated by EM and CAM, and slightly attenuated by RXM. Changes in mRNA expression of E-selectin, P-selectin, ICAM-1, VCAM-1, and TNF-α were associated with the number of neutrophils migrating into the airspace. 14-MRMLs clearly inhibited the induction of VCAM-1 mRNA, and tended to attenuate the induction of ICAM-1 and TNF-α mRNA, but did not inhibit the induction of E-selectin and P-selectin mRNA. Discussion: These findings show that 14-MRMLs clearly attenuated the expression of VCAM-1 mRNA, and tended to attenuate the induction of ICAM-1 and TNF-αmRNA, and subsequently inhibited leucocyte, especially neutrophil migration into the airspace during the early phase of BLM-induced lung injury and finally inhibited lung fibrosis. This might be one potent mechanism of the anti-inflammatory effects of 14-MRMLs in BLM-induced acute lung injury. The findings suggest that prophylactic administration of 14-MRMLs may be clinically efficacious in preventing acute exacerbation of interstitial pneumonia and acute lung injury.

DOI： 10.1272/jnms.69.252

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：EUROPEAN RESPIRATORY SOC JOURNALS LTD  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：英語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：EUROPEAN RESPIRATORY SOC JOURNALS LTD  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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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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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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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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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：EUROPEAN RESPIRATORY SOC JOURNALS LTD  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：日本語   出版者・発行元：日本成人病(生活習慣病)学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：JOHN WILEY & SONS INC  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：英語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

CiNii Books

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

CiNii Books

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

CiNii Books

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

CiNii Books

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記述言語：英語   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Background: In conjunction with allergens, diesel exhaust particles act as an adjuvant to enhance IgE responses, inducing expression of cytokines/chemokines and adhesion molecules, and increasing airway hyper-responsiveness (AHR). As most studies were designed to expose animals to diesel exhaust throughout the periods of both sensitization and allergen challenge, it remains unclear whether diesel exhaust (DE) exposure exaggerates airway responses in asthmatic animals.
Objective: To study effects of exposure to Low-dose DE on AHR and allergic airway inflammation in asthmatic mice.
Methods: BALB/c mice were sensitized by intraperitoneal injection of ovalbumin and challenged by intranasal administration with ovalbumin. They were exposed to tow-dose DE for 7 h/day, 5 days/week, for up to 12 weeks. AHR to methacholine was evaluated by whole-body plethysmography as welt as bronchoalveolar lavage cell analysis and cytokine gene expression in lungs.
Results: Repeated exposure of asthmatic mice to low-dose DE resulted in increased AHR and gene expression of several pro-asthmatic cytokines/chemokines, but these effects rapidly subsided with continued exposure to DE.
Conclusion: Repeated exposure to tow-dose DE after ovalbumin challenge exaggerates allergic responses in mice, but effects are not prolonged with continuous DE exposure. (c) 2006 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.clim.2006.08.003

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本衛生学会  

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記述言語：日本語   出版者・発行元：(公社)大気環境学会  

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記述言語：日本語   出版者・発行元：(公社)大気環境学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(公財)日本感染症医薬品協会  

EM703のSmad3の発現に及ぼす作用についてin vitro,in vivoで検討した.マウス肺線維芽細胞株MLg2908を用いた.また,ICR雄マウスを用い,ブレオマイシン(BLM)は経尾静脈より1回投与し,EM703は1日1回連日経口投与した.MLg2908のSmad3のmRNA発現はTGF-β添加より完全に消失したが,EM703の前添加より完全に回復した.EM703の同時添加と後添加では回復しなかった.BLM投与後7日目の肺組織のSmad3のmRNA発現はBLM投与により著明に減少したが,EM703の併用投与より回復した.EM703はSmad3のネガティブフィードバックループ形成を抑制することにより,TGF-βのシグナル伝達を抑制する役割を果たし,マウスBLM肺線維症モデルにおいて,肺線維症進展を抑制する可能性が示唆された

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記述言語：日本語   出版者・発行元：(公社)大気環境学会  

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記述言語：日本語   出版者・発行元：(公財)日本感染症医薬品協会  

びまん性汎細気管支炎(DPB)に対するエリスロマイシン(EM)の作用は従来の抗菌作用によらず,抗炎症作用によると報告されている.今回,抗菌作用を持たないEMの新規誘導体EM703のマウスブレオマイシン(BLM)肺線維症に対する抗炎症・線維化抑制作用について検討した.マウスBLM肺線維症モデルにおいて,早期の炎症細胞の気腔内への浸潤はEM703投与により抑制された.EM703の前投与による肺線維症予防効果と早期投与による治療効果が認められた.EM703後投与群では線維症抑制効果が認められなかった.BLM肺線維症モデルにおいて,EM703はTGF-βによる肺線維芽細胞増殖・コラーゲン産生を抑制することにより直接肺線維症進展を抑制する可能性が示唆され,抗線維化作用のメカニズムの一つであると考えられた

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

7週齢の雄マウスを用いて生理食塩水に溶解したブレオマイシン100mg/kg,0.3ml/mouseを尾静脈に投与する方法でブレオマイシンによる急性肺傷害における好中球接着浸潤にかかわる分子の発現に関する検討とエリスロマイシン,クラリスロマイシン及びロキシスリマイシンの3種類の14員環マクロライドの作用について検討を行った.その結果,ブレオマイシン急性肺障害に対して14員環マクロライドはVCAM-1,ICAM-1及びTNF-αのmRNA発現を抑制することにより,好中球をはじめとする炎症細胞の肺への浸潤とそれに続発する肺障害を抑制する役割を果たすものと考えられた

DOI： 10.1272/jnms.69.252

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記述言語：英語   出版者・発行元：AMER COLL CHEST PHYSICIANS  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(公財)日本感染症医薬品協会  

ブレオマイシン(BLM)肺線維化評価モデルに対するロキシスロマイシン(RXM),クラリスロマイシン(CAM)の抑制効果を検討し,更にBLM急性肺傷害モデルにおける好中球と血管内皮間接着分子のmRNA発現および14員環マクロライドの抑制作用について経時的に検討した.RXM,CAMはBLM肺線維症に対して抑制効果を有することが確認された.BLM急性肺傷害モデルにおいて,好中球はBLM投与後24時間をピークに気腔内に浸潤し,144時間から264時間まで再浸潤した.CD62EとCD62PのmRNA発現はBLM投与後6時間および12時間に誘導され,一旦消失後48時間から264時間まで再誘導された.一方,VCAM-1の発現はBLM投与後48時間から312時間まで誘導され,この発現は14員環マクロライド投与により著明に抑制された

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER LUNG ASSOC  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本サルコイドーシス  

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