
Received a doctorate in food and nutritional sciences from the University of Shizuoka. Specializes in molecular biology, molecular immunology, and molecular nutrition.
Updated on 2025/01/03
Received a doctorate in food and nutritional sciences from the University of Shizuoka. Specializes in molecular biology, molecular immunology, and molecular nutrition.
Doctor of Food and Nutritional Sciences ( 2002.3 University of Shizuoka )
分子生物学、自然免疫、食品栄養科学
Food and Nutritional Sciences
Life Science / Immunology
Life Science / Food sciences
Life Science / Medical biochemistry
Life Science / Cell biology
Life Science / Molecular biology
University of Shizuoka Graduate School of Nutritional and Environmental Sciences
1999.4 - 2002.3
Nippon Medical School Department of Biochemistry and Molecular Biology, Senior Assistant Professor
2022.10
Country:Japan
Nippon Medical School Assistant Professor
2018.4 - 2022.9
Tokyo Medical and Dental University Medical Research Institute Assistant Professor
2014.4 - 2018.3
Hokkaido University Institute for Genetic Medicine Assistant Professor
2007.8 - 2014.3
Kinki University Faculty of Medicine Assistant Professor
2003.4 - 2007.7
The University of Tokyo Graduate School of Medicine
2002.4 - 2003.3
The Japanese Society of Clinical Nutrition.
2024
The Japanese Society for Virology
2024
Japan Society of Nutrition and Food Science
2022
The Japanese Biochemical Society
Japanese Association for Food Immunology
Sumio Hayakawa, Atsushi Tamura, Nikita Nikiforov, Hiroyuki Koike, Fujimi Kudo, Yinglan Cheng, Takuro Miyazaki, Marina Kubekina, Tatiana V. Kirichenko, Alexander N. Orekhov, Nobuhiko Yui, Ichiro Manabe, Yumiko Oishi
JCI Insight 7 ( 22 ) 2022.11
ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses Reviewed
Sumio Hayakawa, Souichi Shiratori, Hiroaki Yamato, Takeshi Kameyama, Chihiro Kitatsuji, Fumi Kashigi, Showhey Goto, Shoichiro Kameoka, Daisuke Fujikura, Taisho Yamada, Tatsuaki Mizutani, Mika Kazumata, Maiko Sato, Junji Tanaka, Masahiro Asaka, Yusuke Ohba, Tadaaki Miyazaki, Masahiro Imamura, Akinori Takaoka
Nature Immunology 12 ( 1 ) 37 - U56 2011.1
Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence Reviewed
A Takaoka, S Hayakawa, H Yanai, D Stoiber, H Negishi, H Kikuchi, S Sasaki, K Imai, T Shibue, K Honda, T Taniguchi
NATURE 424 ( 6948 ) 516 - 523 2003.7
Apoptosis induction by epigallocatechin gallate involves its binding to Fas Reviewed
S Hayakawa, K Saeki, M Sazuka, Y Suzuki, Y Shoji, T Ohta, K Kaji, A Yuo, M Isemura
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 285 ( 5 ) 1102 - 1106 2001.8
Differential effects of theasinensins and epigallocatechin-3-O-gallate on phospholipid bilayer structure and liposomal aggregation. Reviewed International journal
Asako Narai-Kanayama, Sumio Hayakawa, Takayuki Yoshino, Futa Honda, Hiroko Matsuda, Yumiko Oishi
Biochimica et biophysica acta. Biomembranes 1866 ( 5 ) 184312 - 184312 2024.6
Non-target GC-MS analyses of fecal VOCs in NASH-hepatocellular carcinoma model STAM mice. Reviewed International journal
Mai Kato, Momoka Yamaguchi, Akira Ooka, Ryota Takahashi, Takuji Suzuki, Keita Onoda, Yuko Yoshikawa, Yuta Tsunematsu, Michio Sato, Yasukiyo Yoshioka, Miki Igarashi, Sumio Hayakawa, Kumiko Shoji, Yutaka Shoji, Tomohisa Ishikawa, Kenji Watanabe, Noriyuki Miyoshi
Scientific reports 13 ( 1 ) 8924 - 8924 2023.6
Yinglan Cheng, Ichiro Manabe, Sumio Hayakawa, Yusuke Endo, Yumiko Oishi
Frontiers in Immunology 14 2023.1
Cyclic stretch regulates immune responses via tank‐binding kinase 1 expression in macrophages Reviewed
Anna Nakagawa, Sumio Hayakawa, Yinglan Cheng, Azusa Honda, Ryo Yuzawa, Rei Ogawa, Yumiko Oishi
FEBS Open Bio 2022.12
Sumio Hayakawa, Tomokazu Ohishi, Yumiko Oishi, Mamoru Isemura, Noriyuki Miyoshi
Antioxidants 11 ( 12 ) 2352 - 2352 2022.11
Antitumor effect of memantine is related to the formation of the splicing isoform of GLG1, a decoy FGF‑binding protein. Reviewed International journal
Fumio Yamaguchi, Sumio Hayakawa, Shota Kawashima, Takayuki Asakura, Yumiko Oishi
International journal of oncology 61 ( 1 ) 2022.7
Involvement of microRNA modifications in anticancer effects of major polyphenols from green tea, coffee, wine, and curry. Reviewed International journal
Tomokazu Ohishi, Sumio Hayakawa, Noriyuki Miyoshi
Critical reviews in food science and nutrition 1 - 32 2022.3
Anti-Cancer Effects of Green Tea Epigallocatchin-3-Gallate and Coffee Chlorogenic Acid International journal
Sumio Hayakawa, Tomokazu Ohishi, Noriyuki Miyoshi, Yumiko Oishi, Yoriyuki Nakamura, Mamoru Isemura
Molecules 25 ( 19 ) 4553 - 4553 2020.10
Tea, Coffee and Health Benefits
Sumio Hayakawa, Yumiko Oishi, Hiroki Tanabe, Mamoru Isemura, Yasuo Suzuki
Reference Series in Phytochemistry 991 - 1047 2019
In vitro and in silico studies of the molecular interactions of epigallocatechin-3-o-gallate (egcg) with proteins that explain the health benefits of green tea Reviewed
Koichi Saeki, Sumio Hayakawa, Shogo Nakano, Sohei Ito, Yumiko Oishi, Yasuo Suzuki, Mamoru Isemura
Molecules 23 ( 6 ) 2018
SREBP1 Contributes to Resolution of Pro-inflammatory TLR4 Signaling by Reprogramming Fatty Acid Metabolism Reviewed
Yumiko Oishi, Nathanael J. Spann, Verena M. Link, Evan D. Muse, Tobias Strid, Chantle Edillor, Matthew J. Kolar, Takashi Matsuzaka, Sumio Hayakawa, Jenhan Tao, Minna U. Kaikkonen, Aaron F. Carlin, Michael T. Lam, Ichiro Manabe, Hitoshi Shimano, Alan Saghatelian, Christopher K. Glass
CELL METABOLISM 25 ( 2 ) 412 - 427 2017.2
Constitutive aryl hydrocarbon receptor signaling constrains type I interferon-mediated antiviral innate defense. Reviewed
Yamada T, Horimoto H, Kameyama T, Hayakawa S, Yamato H, Dazai M, Takada A, Kida H, Bott D, Zhou AC, Hutin D, Watts TH, Asaka M, Matthews J, Takaoka A
Nature Immunology 17 687 - 694 2016.4
Anti-Cancer Effects of Green Tea by Either Anti- or Pro- Oxidative Mechanisms. Reviewed International journal
Sumio Hayakawa, Kieko Saito, Noriyuki Miyoshi, Tomokazu Ohishi, Yumiko Oishi, Mamoru Miyoshi, Yoriyuki Nakamura
Asian Pacific journal of cancer prevention : APJCP 17 ( 4 ) 1649 - 54 2016
Stimulation of Macrophages with the beta-Glucan Produced by Aureobasidium pullulans Promotes the Secretion of Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL) Reviewed
Koji Kawata, Atsushi Iwai, Daisuke Muramatsu, Shiho Aoki, Hirofumi Uchiyama, Mitsuyasu Okabe, Sumio Hayakawa, Akinori Takaoka, Tadaaki Miyazaki
PLOS ONE 10 ( 4 ) e0124809 2015.4
Masaki Tabuchi, Sumio Hayakawa, Eiko Honda, Kana Ooshima, Tatsuki Itoh, Koji Yoshida, Ah-Mee Park, Hideaki Higashino, Mamoru Isemura, Hiroshi Munakata
World Journal of Experimental Medicine 3 ( 4 ) 100 - 100 2013
Conditioned media from lung cancer cell line A549 and PC9 inactivate pulmonary fibroblasts by regulating protein phosphorylation Reviewed
Ah-Mee Park, Sumio Hayakawa, Eiko Honda, Yoshihiro Mine, Koji Yoshida, Hiroshi Munakata
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 518 ( 2 ) 133 - 141 2012.2
Subcellular localization of human heparanase and its alternative splice variant in COS-7 cells Reviewed
Mayumi Sato, Kana Amemiya, Sumio Hayakawa, Hiroshi Munakata
CELL BIOCHEMISTRY AND FUNCTION 26 ( 6 ) 676 - 683 2008.8
Cytokine-rich autologous serum system for cartilaginous tissue engineering Reviewed
Noritaka Isogai, Yumiko Nakagawa, Koji Suzuki, Ryo Yamada, Shinichi Asamura, Sumio Hayakawa, Hiroshi Munakata
ANNALS OF PLASTIC SURGERY 60 ( 6 ) 703 - 709 2008.6
Effects of decorin on the expression of alpha-smooth muscle actin in a human myofibroblast cell line Reviewed
Tatsuya Nakatani, Eiko Honda, Sumio Hayakawa, Mayumi Sato, Ken Satoh, Masatoshi Kudo, Hiroshi Munakata
MOLECULAR AND CELLULAR BIOCHEMISTRY 308 ( 1-2 ) 201 - 207 2008.1
Combination therapy with PEG-IFN-α and 5-FU inhibits HepG2 tumour cell growth in nude mice by apoptosis of p53 Reviewed
S. Hagiwara, M. Kudo, T. Nakatani, Y. Sakaguchi, M. Nagashima, N. Fukuta, M. Kimura, S. Hayakawa, H. Munakata
British Journal of Cancer 97 ( 11 ) 1532 - 1537 2007.12
Oxidized LDL binding to LOX-1 upregulates VEGF expression in cultured bovine chondrocytes through activation of PPAR-gamma Reviewed
Sohya Kanata, Masao Akagi, Shunji Nishimura, Sumio Hayakawa, Kohji Yoshida, Tatsuya Sawamura, Hiroshi Munakata, Chiaki Hamanishi
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 348 ( 3 ) 1003 - 1010 2006.9
DNA microarray analysis of changes in gene expression induced by 1,25-dihydroxyvitamin D-3 in human promyelocytic leukemia HL-60 cells Reviewed
Takuji Suzuki, Hideaki Tazoe, Kyoko Taguchi, Yu Koyama, Hiroyasu Ichikawa, Surnio Hayakawa, Hiroshi Munakata, Mamoru Isemura
BIOMEDICAL RESEARCH-TOKYO 27 ( 3 ) 99 - 109 2006.6
1,25-dihydroxyvitamin D-3 suppresses exportin expression in human promyelocytic leukemia HL-60 cells Reviewed
Takuji Suzuki, Yu Koyama, Sumio Hayakawa, Hiroshi Munakata, Mamoru Isemura
BIOMEDICAL RESEARCH-TOKYO 27 ( 2 ) 89 - 92 2006.4
Hypoxia-induced hyaluronan synthesis by articular chondrocytes: the role of nitric oxide Reviewed
K Hashimoto, K Fukuda, K Yamazaki, N Yamamoto, T Matsushita, S Hayakawa, H Munakata, C Hamanishi
INFLAMMATION RESEARCH 55 ( 2 ) 72 - 77 2006.2
1,25-Dihydroxyvitamin D-3 suppresses gene expression of eukaryotic translation initiation factor 2 in human promyelocytic leukemia HL-60 cells Reviewed
T Suzuki, Y Koyama, H Ichikawa, K Tsushima, K Abei, S Hayakawa, R Kuruto-Niwa, R Nozawa, M Isemura
CELL STRUCTURE AND FUNCTION 30 ( 1-2 ) 1 - 6 2005.12
Combined chondrocyte-copolymer implantation with slow release of basic fibroblast growth factor for tissue engineering an auricular cartilage construct Reviewed
N Isogai, T Morotomi, S Hayakawa, H Munakata, Y Tabata, Y Ikada, H Kamiishi
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 74A ( 3 ) 408 - 418 2005.9
Effects of tea constituents on cell cycle progression of human leukemia U937 cells Reviewed
Masahiko Ohata, Yu Koyama, Takuji Suzuki, Sumio Hayakawa, Koichi Saeki, Yoshiyuki Nakamura, Mamoru Isemura
BIOMEDICAL RESEARCH-TOKYO 26 ( 1 ) 1 - 7 2005.2
Role of the heme regulatory motif in the heme-mediated inhibition of mitochondrial import of 5-aminolevulinate synthase Reviewed
H Munakata, JY Sun, K Yoshida, T Nakatani, E Honda, S Hayakawa, K Furuyama, N Hayashi
JOURNAL OF BIOCHEMISTRY 136 ( 2 ) 233 - 238 2004.8
Oxidized low-density lipoprotein (ox-LDL) binding to lectin-like ox-LDL receptor-1 (LOX-1) in cultured bovine articular chondrocytes increases production of intracellular reactive oxygen species (ROS) resulting in the activation of NF-kappa B Reviewed
S Nishimura, M Akagi, K Yoshida, S Hayakawa, T Sawamura, H Munakata, C Hamanishi
OSTEOARTHRITIS AND CARTILAGE 12 ( 7 ) 568 - 576 2004.7
Identification of 6-methylsulfinylhexyl isothiocyanate as an apoptosis-inducing component in wasabi Reviewed
M Watanabe, M Ohata, S Hayakawa, M Isemura, S Kumazawa, T Nakayama, M Furugori, N Kinae
PHYTOCHEMISTRY 62 ( 5 ) 733 - 739 2003.3
Inhibition of carcinogenesis by tea aqueous non-dialyzates fractionated from crude tea extracts Reviewed
Y Nakamura, M Isemura, S Hayakawa, K Saeki, Y Koyama, T Kimura, M Kuroyanagi, T Noro, K Yoshino, T Tsuneyoshi
FOOD FACTORS IN HEALTH PROMOTION AND DISEASE PREVENTION 851 381 - 389 2003
Identification of licocoumarone as an apoptosis-inducing component in licorice. Reviewed
Watanabe M, Hayakawa S, Isemura M, Kumazawa S, Nakayama T, Mori C, Kawakami T
Biological and Pharmaceutical Bulletin 25 ( 10 ) 1388 - 1390 2002.8
Apoptosis induction by lectin isolated from the mushroom Boletopsis leucomelas in U937 cells Reviewed
Y Koyama, Y Katsuno, N Miyoshi, S Hayakawa, T Mita, H Muto, S Isemura, Y Aoyagi, M Isemura
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 66 ( 4 ) 784 - 789 2002.4
Apoptosis induction associated with cell cycle dysregulation by rice bran agglutinin Reviewed
N Miyoshi, Y Koyama, Y Katsuno, S Hayakawa, T Mita, T Ohta, K Kaji, M Isemura
JOURNAL OF BIOCHEMISTRY 130 ( 6 ) 799 - 805 2001.12
Apoptosis-inducing activity of high molecular weight fractions of tea extracts Reviewed
S Hayakawa, T Kimura, K Saeki, Y Koyama, Y Aoyagi, T Noro, Y Nakamura, M Isemura
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 65 ( 2 ) 459 - 462 2001.2
Apoptosis-inducing activity of galloyl monosaccharides in human histiocytic lymphoma U937 cells Reviewed
Saeki, I, S Hayakawa, T Noro, T Miyase, Y Nakamura, K Tanji, S Kumazawa, T Nakayama, M Isemura
PLANTA MEDICA 66 ( 2 ) 124 - 126 2000.3
Importance of a pyrogallol-type structure in catechin compounds for apoptosis-inducing activity Reviewed
K Saeki, S Hayakawa, M Isemura, T Miyase
PHYTOCHEMISTRY 53 ( 3 ) 391 - 394 2000.2
Tea catechins and related polyphenols as anti-cancer agents Reviewed
M Isemura, K Saeki, T Kimura, S Hayakawa, T Minami, M Sazuka
BIOFACTORS 13 ( 1-4 ) 81 - 85 2000
Tea, Coffee and Health Benefits Bioactive Molecules in Food
Hayakawa S, Oishi Y, Tanabe H, Isemura M, Suzuki Y(pp.1-58)
Springer International Publishing AG 2018
Health benefits of tea consumption, Beverage Impacts on Health and Nutrition
Takuji Suzuki, Noriyuki Miyoshi, Sumio Hayakawa, Shinjiro Imai, Mamoru Isemura, Yoriyuki Nakamura(pp 49-67)
Springer International Publishing, Switzerland 2016
栄養 評価と治療/緑茶成分によるアポトーシス関連分子の発現調節
伊勢村護, 早川清雄(20(3):43-47)
メディカルレビュー社 2003
ZAPSは抗ウイルス応答において活性化されるRIG-Iの強力な調節因子である Invited
早川清雄, 亀山武志, 高岡晃教
新着論文レビュー (First Author's) 2011
Immune Function Activation by Green Tea Catechin
Sumio Hayakawa, Asako Narai-Kanayama, Takeshi Kameyama, Taku Sato
12th Annual Meeting of the International Cytokine & Interferon Society (ICIS) 2024.10
細胞内コレステロールはマクロファージの炎症応答を制御する
早川清雄, 大石由美子
第46回日本臨床栄養学会総会・第45回日本臨床栄養協会総会 第22回大連合大会 2024.10
茶カテキンによる免疫機能活性化における基盤的研究
早川清雄, 奈良井 朝子, 亀山武志
第78回 日本栄養・食糧学会 2024.5
Cellular cholesterol enhances Myd88-mediated signalling in inflammatory responses
Sumio Hayakawa, Yinglan Cheng, Yumiko Oishi
the 47th FEBS Congress 2023.7
細胞内コレステロールの制御による抗HSV-1効果の解析
新谷雄太郎, 早川清雄, 大倉定之, 田村篤志, 大石由美子, 佐藤卓
第71回日本ウイルス学会学術集会 2024.11
炎症応答におけるマウスNEDD4の機能解析
安岡璃奈, 銭博聞, 早川清雄, 佐藤卓
第 92 回日本医科大学医学会総会・学術集会 2024.9
マクロファージにおけるコレステロールを介した炎症応答と制御メカニズム
早川 清雄, 成 英瀾, 大石 由美子
第77回 日本栄養・食糧学会大会 2023.7
エピガロカテキンガレート酸化物とリン脂質二重層との相互作用
奈良井朝子, 早川清雄, 吉野尊之, 本多風太, 松田寛子, 大石由美子
日本食品科学工学会 関東支部大会 2023.3
Cellular cholesterol contributes to the innate immune response via Myd88
Sumio Hayakawa, Atsushi Tamura, Yinglan Cheng, Yumiko Oishi
JSICR/MMCB 2022 Joint Symposium
自然免疫応答の調節機構
早川清雄, 大石由美子
東京医科歯科大学 免疫学・病態生化学領域合同シンポジウム 2017.3
ZAPSトランスジェニックマウスを用いた自然免疫応答の解析
早川清雄, 大和弘明, 白鳥聡一, 山田大翔, 亀山武志, 数馬田美香, 宮崎忠明, 高岡晃教
日本ウイルス学会 北海道支部会 第45回 夏期シンポジウム 2011.7
自然免疫系における核酸認識受容体を介したシグナルの新規調節因子と抗ウイルス作用
亀山武志, 早川清雄, 白鳥聡一, 大和弘明, 北辻千展, 樫木芙美, 後藤翔平, 亀岡章一郎, 藤倉大輔, 水谷龍明, 数馬田美香, 佐藤麻衣子, 今村雅寛, 浅香正博, 大場雄介, 宮崎忠昭, 高岡 晃教
第58回日本ウイルス学会 2010.11
炎症シグナルが調節する脂質代謝調節機構
早川清雄, 大石由美子
第6回Molecular Cardiovascular Conference II 2015.9
ZAPSが担う自然免疫活性化のメカニズム
早川清雄, 髙岡晃教
,平成23年度 北海道大学遺伝子病制御研究所 共同研究集会 2011.12
Identification of a potent stimulator of RIG-I mediated signaling for antiviral response.
Chihiro Kitatsuji, Sumio Hayakawa, Souichi Shiratori, Hiroaki Yamato, Takeshi Kameyama, Fumi Kashigi, Showhey Goto, Shouichiro Kameoka, Yusuke Ohba, Tadaaki Miyazaki, Akinori Takaoka
Biochemistry and Molecular Biology 2010
自然免疫におけるIFN 応答の新たな制御メカニズム
早川清雄, 白鳥聡一, 大和弘明, 後藤翔平, 樫木芙美, 亀山武志, 髙岡晃教
第32回日本分子生物学会年会 2009.12
Regulation of cytosolic nucleic acid-activated innate responses by the IFN-inducible protein SCI2
S. Hayakawa, S. Shiratori, H. Yamato, T. Kameyama, C. Kitatsuji, F. Kashigi, S. Goto, S. Kameoka, M. Sato, M. Kazumata, T. Miyazaki, Y. Ohba, A. Takaoka
The 14th International Congress of Immunology, 2010.8
自然免疫系の核酸認識受容体を介するシグナルの新規調節因子と抗ウイルス作用
亀山武志, 早川清雄, 白鳥聡一, 大和弘明, 高岡晃教
日本ウイルス学会 北海道支部会 第44回 夏期シンポジウム 2010.7
細胞質内核酸による自然免疫活性化機構
早川清雄, 白鳥聡一, 大和弘明, 亀山武志, 北辻千展, 亀岡章一郎, 後藤翔平, 樫木芙美, 数馬田美香, 佐藤麻衣子, 大場雄介, 宮崎忠明, 高岡晃教
第47回日本生化学会北海道支部例会
SCI2 を介した自然免疫応答制御
髙岡晃教, 早川清雄
第82回日本生化学会大会 2009.10
茶カテキン酸化物に特異的な生理活性に及ぼす茶飲料中ビタミンCの影響に関する解析
Grant number:24K08772 2024.4 - 2027.3
日本学術振興会 科学研究費助成事業 基盤研究(C)
奈良井 朝子, 早川 清雄
Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )
Fundamental Research on the Role of Ketone Bodies and Their Control Methods in Eating Disorders
Grant number:24K10717 2024.4 - 2027.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )
細胞内コレステロールを基軸とした炎症慢性化の基盤的研究
Grant number:21H03366 2021.4 - 2025.3
日本学術振興会 科学研究費助成事業 基盤研究(B) 基盤研究(B)
早川 清雄, 田村 篤志
Grant amount:\16770000 ( Direct Cost: \12900000 、 Indirect Cost:\3870000 )
脂質は、効率のよいエネルギー源となるのみならず、ホルモンや細胞膜の材料として必須な因子であると同時に、その代謝異常(脂質異常症)は動脈硬化症・糖尿病・慢性腎臓病などの疾患と密接に関わっていることが明らかとなっている。本課題においては、病態の発症や進展と密接に関連するマクロファージに着目し、マクロファージ内のコレステロールが、TLRs-Myd88経路を介する炎症反応をダイレクトに制御(活性化)するメカニズムの解明を目指している。細胞内に蓄積するコレステロールを、慢性炎症の新たな調節因子と位置づけ、細胞内コレステロールを軸とした炎症誘導メカニズムを理解し、マクロファージの細胞内コレステロールを標的とした動脈硬化治療や予防につなげる基盤的研究を進めた。まず、LPS刺激による炎症応答がコレステロールトランスポーターの阻害剤で炎症応答が増強されたことから、細胞内のコレステロールの排泄を促進する薬剤としてポリロタキサン(PRX)を用いて、炎症応答との関連を解析した。その結果、LPSによって誘導される炎症性サイトカインであるIL6やIL1b mRNA発現が有意に抑制された。次に、PRX処理後の細胞コレステロールをGC-MSで解析した結果、炎症応答に相関して有意に抑制された。さらに、炎症応答の鍵となる転写因子NF-kBの活性化を免疫蛍光染色法で解析すると、NF-kBの核移行が抑制された。これらの結果から、炎症応答に伴い活性化されるサイトカインは、細胞内コレステロールと密接に連携し炎症応答を制御していることが示唆された。
超分子を用いた腫瘍随伴マクロファージのリプログラミングと腫瘍成育微小環境の破壊
Grant number:20H04527 2020.4 - 2024.3
日本学術振興会 科学研究費助成事業 基盤研究(B) 基盤研究(B)
田村 篤志, 早川 清雄
Grant amount:\17680000 ( Direct Cost: \13600000 、 Indirect Cost:\4080000 )
がん免疫療法は臨床的に優れたがんの治療効果を示すものの、奏効率が30%程度と低いことが課題と考えられている。近年では、PD-1/PD-L1などの免疫回避機構以外にも、がん周辺環境が免疫回避にとって重要だと考えられている。本研究では、がん免疫の抑制やがん生育環境の構築を通じてがんの増殖に有利な環境を作ることに寄与している腫瘍随伴マクロファージ(TAM)に着目し、TAMの代謝に介入することで細胞機能のリプログラミングやがん免疫療法の治療効果増強が可能か検討する。本研究課題では、細胞内のコレステロール代謝に介入することが可能なシクロデキストリン含有ポリロタキサンを用いて、コレステロール代謝の調節とTAMの機能の変化について検討する。
2021年度の研究では前年度に合成法を確立したペプチド修飾ポリロタキサンの機能評価、および担癌モデルマウスをもちいた抗がん作用の評価を行った。オリゴエチレングリコールを化学修飾し水溶化したポリロタキサンを担癌モデルマウスに投与したが、高用量でも抗がん作用は確認されなかった。水溶性ポリロタキサンは高濃度でも細胞毒性を示さないというこれまでの知見と合致する結果である。同様に、細胞障害性を有するメチル化ポリロタキサンも抗がん作用は示さなかったが、がん細胞を標的とする機能分子を修飾することで、抗癌作用を示すことが明らかとなった。本結果は、がん組織に対する標的指向性をポリロタキサンに賦与する必要があることを示唆している。今後はTAMに対する標的指向性を賦与したポリロタキサンの機能評価を実施する。
Analysis of lipid metabolism regulation through chronic inflammation
Grant number:16K00848 2016.4 - 2019.3
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)
Hayakawa Sumio
Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )
Inflammatory responses play a central role, as the front line, in the host defense against injury and infection. Under healthy conditions, acute inflammation can be resolved by means of an active termination program. Chronic inflammation is considered a risk factor for the development of pathological conditions, but the precise mechanism of their association is currently unknown. Recent studies have identified a link between inflammatory signaling and lipid signaling. In this study, we hypothesize that TLR-4 signaling activates an SREBP-mediated process through the inflammatory caspase and leads to elevated cholesterol synthesis in macrophages. Our study would provide new insight into the molecular mechanism of crosstalk between chronic inflammation and lipid metabolism signaling and offer new opportunities for the development of drug targets that ameliorate chronic inflammation.
Activation of innate immune response by DNA from food
Grant number:26560052 2014.4 - 2017.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research
HAYAKAWA Sumio
Grant amount:\3640000 ( Direct Cost: \2800000 、 Indirect Cost:\840000 )
Food is recognized as one of the important factors which regulate human health such as immune response. It is known that vitamins, minerals and proteins are essential nutrients to build a healthy body. However, the role of food DNA on health is not clearly understood. So, we focused on the effect of food DNA on activation of innate immune signaling pathway mediated by PRRs. Here we show that a complex with the food DNA and short peptide, the only cathelicidin-derived antimicrobial peptide, activated innate immune response and functioned as a ligand of RIG-I in macrophage. We suggest that DNA from food could provide an application in therapy aimed at maintaining good health.
Novel mechanisms of cellular antiviral defense through the PARP-13 shorter isoform, ZAPS
Grant number:25713032 2013.4 - 2017.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A) Grant-in-Aid for Young Scientists (A)
HAYAKAWA Sumio
Grant amount:\25090000 ( Direct Cost: \19300000 、 Indirect Cost:\5790000 )
Type I IFN are produced in response to viral infection and are key cytokines for the activation of innate immunity. The pathogen invasion is sensed by pattern-recognition receptors(PRRs) of innate immune system through the recognition of pathogen associated molecular patterns(PAMPs). The PRRs trigger the activation of intracellular signaling pathway, which leads to the induction of antimicrobial genes. RIG-I is the key PRR for detection of positive- and negative strand RNA viruses in the cytoplasm of cells and has an important triggering response to viruses, such as influenza A virus. However, the NS1 from influenza virus counters host antiviral defenses. In this study, the interaction of RIG-I and ZAPS is one of the keypoints, wherein NS1 inhibits RIG-I-mediated antiviral activity.
The study of activation of innate immune response by dietary nucleic acids via oral mucosa
Grant number:23617001 2011 - 2013
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)
KAMEYAMA Takeshi, HAYAKAWA Sumio, ADACHI Yoshihiro Christopher, TAKAOKA Akinori, OKADA Kanako, TODA Haruka
Grant amount:\5330000 ( Direct Cost: \4100000 、 Indirect Cost:\1230000 )
Diet contains various kinds of nutrient,, which keep us healthy. However the nutritional role of nucleic acids derived from diets is not clearly understood. The innate immunity system is an essential step as the front line of host defense. Although oral mucosa acts as powerful barriers, the importance of oral mucosa in innate immunity remains unclear. In this study, we demonstrate that DNA derived from vegetable activated innate immune response both in vitro and in vivo, which may provide the nutritional immunological role of dietary nucleic acids.
Analysis of the innate immune response to nucleic acids in tumor cells.
Grant number:23650586 2011 - 2012
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research
HAYAKAWA Sumio, KAMEYAMA Takeshi, ADACHI Yoshihiro Christopher
Grant amount:\3640000 ( Direct Cost: \2800000 、 Indirect Cost:\840000 )
Pattern recognition receptors (PRRs)-mediated activation of the innate immune response is triggered by recognition of pathogen-associated molecular patterns (PAMPs), such as a various bacterial cell wall components, peptidoglycan and lipoprotein, as well as bacterial and viral nucleic acids. In this study, we demonstrate that nucleic acids are recognized by PRRs in some tumor types, and promoted the activation of IRF and NF-kB pathway. However, some types of tumor cells are not activated. Furthermore, we are able to find the relationship between the tissue specificity of innate immune response and apoptosis induction. In in vivo experiment, nucleic acids inhibit growth of transplantation tumor in nude mice. Thus, these finding indicate that nucleic acids may contribute to the progress of material for therapeutic cancer. We consider clarifying the detail mechanism of nucleic acids recognition on innate immune response from the molecular, biochemical and cell biology viewpoints.
Basic studies of protective immunity and immune response on catechins.
Grant number:20680035 2008 - 2009
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A) Grant-in-Aid for Young Scientists (A)
HAYAKAWA Sumio
Grant amount:\10660000 ( Direct Cost: \8200000 、 Indirect Cost:\2460000 )
Green tea, one of the most popular beverage consumed in japan, contains a series of polyphenols known as catechins. The catechins have been reported to posses various biological and pharmacological effects, such as anticancer and antibacterial activities, and lowering of plasma lipids and glucose level. The present study was designed to examine the effect of catechins on the innate immune response. Virus infection elicits potent cellular responses that contain virus spread before the adaptive immune system can intervene, and production of type I interferons (IFN α/β) is central to this process. The sensor involved in coupling recognition of virus infection with the induction of IFN α/β have recently been discovered. These sensors include RIG-I and MDA5, RNA-binding DExD/H box helicases. Recent study indicated that cytosolic DNA-dependent RNA polymerase III converts pathogen dsDNA into dsRNA that has a 5' triphosphate (3pRNA). This RNA species is then sensed by the RNA sensor RIG-I, leading to INF-β production and activation of innate immunity. In this experiments, we found that new function molecule "SCI-2" enhanced the innate immune responses by 3pRNA. These results suggest that SCI-2 is important in recognition of nucleic acids derived from virus. Furthermore, to reveal the underlying mechanisms of action at a molecular level correlation between catechins and SCI-2, we will examine the effect of tea catechin on the virus infection in transgenic mouse.
Grant number:18550102 2006 - 2008
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)
HOSOKAWA Takahiro, SAZUKA Masaki, HAYAKAWA Kiyoo
Grant amount:\4150000 ( Direct Cost: \3700000 、 Indirect Cost:\450000 )
Proteomic a-myofibroblastnalysis of activated- and inactivated
Grant number:18590873 2006 - 2007
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)
MUNAKATA Hiroshi, MATSUDA Toshirou, HAYAKAWA Sumio, YOSHIDA Koji, SAITO Akio
Grant amount:\3830000 ( Direct Cost: \3500000 、 Indirect Cost:\330000 )
Previously we showed that the expression of integrin aω, β1, β3 in MRC-5 cells increased by TGF-β. Increased expression of fibronectin and focal adhesion kinase was also shown. Here, we show the results of proteomics analysis of activation and inactivation of myofibroblast cell line, MRC-5. Transforming growth factor-b stimulated MRC-5 cell extract was compared with that from non-stimulated cells. Several proteins differentially expressed between stimulated and non-stimulated cells including actin-bindin proteins and molecular chaperones.
As previously reported the culture supernatant of A-549 inactivates myofibroblast MRC-5. RNA was obtained from MRC-5 cells after inactivation by the conditioned medium of A-549 and the expressions were analyzed using low density arrays. Expression of some proteins concerned in cell protrusions was increased. The cells treated with forskolin were subjected to proteome analysis. Inceased expression of actin capping protein was observed.
These results, together with previous our findings, suggests that signal transduction mediated by interantions between extracellular matrix and integrins are important in activation and inactivation of myofibroblasts.
Research for the medical treatment of organic fibrosis by controlling the protein interacting with connective tissue growth factor
Grant number:16591000 2004 - 2006
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)
YOSHIDA Koji, SAITO Akio, HAYAKAWA Sumio, NAKATANI Tatsuya
Grant amount:\3300000 ( Direct Cost: \3300000 )
Connective tissue growth factor (CTGF) is a member of the CCN family of the cysteine-rich proteins and involved in wound healing and fibrosis. We have previously shown a biochemical interaction between the CTGF and fibronectin (FN) using the yeast two-hybrid system. In this study, we confirmed the interaction between the CTGF and FN using the surface plasmon resonance (SPR) and solid-phase binding analysis. Our results show that the regions containing the FN type I repeat modules (the N-terminal fibrin, the gelatin-collagen and the C-terminal fibrin binding domains) of FN and the C-terminal domain of CTGF are required for the interaction. We also demonstrated that CTGF enhances the affinity of FN to fibrin. It appears that CTGF contributes to the extracellular matrix accumulation in wound healing and tissue fibrosis by enhancing the affinity of FN to fibrin. Because CTGF is up-regulated during the tissue repair and in coagulation cascade-associated fibrotic disorders, the new function of CTGF found in this study is consistent with its physiological role."
肺線維化における細胞活化抑制メカニズムの解析
Grant number:16790458 2004 - 2006
日本学術振興会 科学研究費助成事業 若手研究(B) 若手研究(B)
早川 清雄
Grant amount:\3300000 ( Direct Cost: \3300000 )
肺ガン細胞の培養上清の精製
10%FBS-DMEMで肺ガン細胞A549を培養したconditioned meiumに、肺線維芽細胞MRC-5の形態変化を誘導する物質をこれまでに見いだした。本年度は、その培養上清を、様々な逆相カラムで分画し、活性を調べたところ、C18カラムと相互作用をもつ活性物質を得ることができた。そこで、最初にオープンカラムを使ってC18カラムと相互作用する物質を精製し、さらに細かく分画するため、HPLCを用いて分析と分取をおこなった。分析の結果から、A549の培養時間に依存して、増加するピークを見いだすことができた。その増加するピークを分取し、活性を測定したところ、MRC-5の形態変化の誘導とα-SMAの発現を抑制する効果が見られた。現在は、その物質を大量に分取し、マススペクトロメトリーによる分子量の測定とNMRを用いた構造解析を行っている。
筋線維芽細胞のタンパク質発現変化
これまでの結果から、A549のconditioned mediumで肺線維芽細胞MRC-5を培養すると増殖が抑制され、細胞周期停止が誘導されることがわかった。また、その時に細胞周期停止に関連するタンパク質p21の発現が増加した。今回、A549のconditioned mediumから精製した物質を用いて、同様な活性があるかどうかを調べると、精製した物質が早期にMRC-5の細胞周期を停止させ、p21の発現増加を誘導した。この結果から、精製した物質はA549のconditioned medium中で働いている主な活性物質であることが考えられた。今後、この物質を用いて、細胞内のタンパク質発現について詳細に調べていきたいと考える。
Constituent substances of living body
Constituent substances of living body
Biochemistry
Experiments in Biochemistry
Research training for student
Institution:Nippon Medical School
Scientist For a Day program 2024 (for young minds aged 10-12)
Role(s): Lecturer
Bunkyo Academy Foundation 2024.7
長野市立 更北中学校【総合的な学習の時間・職場体験講座】
Role(s): Lecturer
長野市立 更北中学校 2023.12
平成28年度 東京医科歯科大学/高大連携プログラム
Role(s): Lecturer
東京医科歯科大学 2016.8
北海道大学 遺伝子病制御研究所 一般公開
Role(s): Planner, Organizing member
北海道大学 2013.6
かなんこども教室【小学生】
Role(s): Lecturer
大阪府南河内郡河南町教育委員会 2003.4 - 2007.7
Gastroenterology Report
Role(s): Peer review
2024.7
PharmaNutrition
Role(s): Peer review
2024.3
Biochemistry and Biophysics Reports
Role(s): Peer review
2024.3
Biochemistry and Biophysics Reports
Role(s): Peer review
2024.1
Gastroenterology Report
Role(s): Peer review
2024.1
Journal of Functional Foods
Role(s): Peer review
2023.12
Food Bioscience
Role(s): Peer review
2023.11
Journal of Functional Foods
Role(s): Peer review
2023.10
Food Bioscience
Role(s): Peer review
2023.9
Cytokine
Role(s): Peer review
2023.7
Food Bioscience
Role(s): Peer review
2023.6
Scientific Reports
Role(s): Peer review
2023.6
Cytokine
Role(s): Peer review
2023.6