NEGATIVE REGULATION OF INFLAMMATORY RESPONSE BY HEAT SHOCK TRANSCRIPTION FACTOR

• Project/Area Number: 19390088
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Yamaguchi University
• Principal Investigator: NAKAI Akira Yamaguchi University, 大学院・医学系研究科, 教授 (60252516)
• Co-Investigator(Kenkyū-buntansha): FUJIMOTO Mitsuaki 山口大学, 大学院・医学系研究科, 講師 (80359900) ; 井上 幸江 山口大学, 大学院・医学系研究科, 講師 (60159978)
• Co-Investigator(Renkei-kenkyūsha): INOUYE Sachiye 安田女子大学, 薬学部, 教授 (60159978)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000); Fiscal Year 2008: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2007: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
• Keywords: 熱ショック / タンパク質 / 転写 / クロマチン / 炎症 / サイトカイン / 転写因子 / 蛋白質 / マウス

Research Abstract

細菌感染や様々な病気は炎症性遺伝子群の誘導と体温上昇からなる発熱反応をひき起こす。発熱は予後を良くする因子であるがその分子機構は十分に明らかにされていない。本研究では、温熱ストレスに対する細胞の主要な応答機構である熱ショック応答と炎症反応の接点について解析を行った。炎症性遺伝子群の誘導は主にIL-6遺伝子の働きによって発熱をひき起こすが、温熱ストレスを感知する熱ショック転写因子が大多数の炎症性遺伝子群の発現誘導を負に制御する分子機構を明らかにした。

Research Products

• [Journal Article] Molecular basis for SUMOylation-dependent regulation of DNA binding activity of Heat Shock Factor 2. (2009)
  • Author(s): Y. Tateishi, M. Ariyoshi, R. Igarashi, H. Hara, K. Mizuguchi, A. Seto, A. Nakai, T. Kokubo, H. Tochio, and M. Shirakawa
  • Journal Title: J. Biol. Chem. 284 Pages: 2435-2447
  • Peer Reviewed
• [Journal Article] Molecular basis for SUMOylation-dependent regulation of DNA binding activity of Heat shock Factor 2 (2009)
  • Author(s): Y. Tateishi, et. al
  • Journal Title: J. Biol. Chem. 284 Pages: 2435-2447
  • Peer Reviewed
• [Journal Article] Analysis of HSF4 binding regions reveals its necessity for gene regulation during development and heat shock response in mouse lenses (2008)
  • Author(s): M.Fujimoto, K.Oshima, T.Shinkawa, B.Wang, S.Inouye, N.Hayashida, R.Takii, and A.Nakai
  • Journal Title: J. Biol. Chem. 283 Pages: 29961-29970
  • Peer Reviewed
• [Journal Article] Functional stabilization of Kv1.5 protein by Hsp70 inmammalian cell lines (2008)
  • Author(s): Y. Hirota, M. Kato, T. Notsu, S. Koshida, T. Inoue, Y. Kawata, J. Miake, U. Bahrudin, P. Li, Y. Hoshikawa, Y. Yamamoto, O. Igawa, Y. Shirayoshi, A. Nakai, H. Ninomiya, K. Higaki, M. Hiraoka, and I. Hisatome
  • Journal Title: Biochem. Biophy. Res. Commun 372 Pages: 469-474
  • Peer Reviewed
• [Journal Article] Attenuation of progressive hearing loss in a model of age-related hearing loss by a heat shock protein inducer, Geranylgeranylacetone (2008)
  • Author(s): T. Mikuriya, K. Sugahara, K. Sugimoto, M. Fujimoto, T. Takemoto, M. Hashimoto, Y. Hirose, H. Shimogori, N. Hayashida, S. Inouye, A. Nakai, H. Yamashita
  • Journal Title: Brain Research 1212 Pages: 9-17
  • Peer Reviewed
• [Journal Article] Attenuation of progressive hearing loss in a model of age-related hearing loss by a heat shock protein inducer, Geranylger anylacetone (2008)
  • Author(s): T. Mikuriya, et. al
  • Journal Title: Brain Research 1212 Pages: 9-17
  • Peer Reviewed
• [Journal Article] Functional stabilization of Kv1.5 protein by Hsp70 in mamma lian cell lines (2008)
  • Author(s): Y. Hirota, ct. al
  • Journal Title: Biochem. Biophy. Res. Commun. 372 Pages: 469-474
  • Peer Reviewed
• [Journal Article] Analysis of HSF4 binding regions reveals its necessity forgene regulation during development and heat shock response in mouse lenses (2008)
  • Author(s): M . Fujimoto, et. al
  • Journal Title: J. Biol. Chem. 283 Pages: 29961-29970
  • Peer Reviewed
• [Journal Article] Heat shock transcription factor 1 is required for maintenance of ciliary beating in mice (2007)
  • Author(s): E. Takaki, M. Fujimoto, T. Nakahari, S. Yonemura, Y. Miyata, N. Hayashida, K. Yamamoto, R.B. Vallee, T. Mikuriya, K. Sugahara, H. Yamashita, S. Inouye, and A. Nakai
  • Journal Title: J. Biol. Chem 282 Pages: 37285-37292
  • Peer Reviewed
• [Journal Article] HSF1 opens chromatin structure of IL-6 promoter to facilitate binding of an activator or a repressor (2007)
  • Author(s): S. Inouye, M. Fujimoto, T. Nakamura, E. Takaki, N. Hayashida, T. Hai, and A. Nakai
  • Journal Title: J. Biol. Chem 282 Pages: 33210-33217
  • Peer Reviewed
• [Journal Article] Genetic evidence for a protective role for heat shock factor 1 and heat shock protein 70 against colitis (2007)
  • Author(s): K.Tanaka, T.Namba, Y.Arai, M.Fujimoto, H.Adachi, G.Sobue, K.Takeuchi, A.Nakai, and T.Mizushima
  • Journal Title: J. Biol. Chem 282 Pages: 23240-23252
  • Peer Reviewed
• [Journal Article] Association of heat shock protein 70 induction and the amelioration of experimental autoimmune uveoretinitis in mice (2007)
  • Author(s): H.Kitamei, N.Kitaichi, K.Yoshida, A.Nakai, M.Fujimoto, M.Kitamura, K.Iwabuchi, A.Miyazaki, K.Namba, S.Ohno, and K.Onoe
  • Journal Title: Immunobiology 212 Pages: 11-18
  • Peer Reviewed
• [Journal Article] Genetic evidence for a protective role of heat shock factor 1 against irritant-induced gastric lesions (2007)
  • Author(s): K. Tanaka, S. Tsutsumi, Y. Arai, T. Hoshino, K. Suzuki, E. Takai, T. Itoh, K. Takeuchi, A. Nakai, and T. Mizushima
  • Journal Title: Mol. Pharmacol 71 Pages: 985-993
  • Peer Reviewed
• [Journal Article] The induction mechanism of the molecular chaperone HSP70 in the gastric mucosa by Geranylgeranylacetone (HSP-inducer) (2007)
  • Author(s): M.Otaka, S.Yamamoto, K.Ogasawara, Y.Takaoka, S.Noguchi, T.Miyazaki, A.Nakai, M.Odashima, T.Matsuhashi, S.Watanabe, and H.Itoh
  • Journal Title: Biochem. Biophy. Res. Commun 353 Pages: 399-404
  • Peer Reviewed
• [Journal Article] HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function) (2007)
  • Author(s): T.Uchiyama, H.Atsuta, T.Utsugi, M.Oguro, A.Hasegawa, T.Nakamura, A.Nakai, M.Nakata, I.Maruyama, H.Tomura, F.Okajima, S.Tomono, S.Kawazu, R.Nagai, M.Kurabayashi
  • Journal Title: Atherosclerosis 190 Pages: 321-329
  • Peer Reviewed
• [Journal Article] Heat shock transcription factor 1 is required for maintenance of ciliary beating in mice. (2007)
  • Author(s): E. Takaki, et. al.
  • Journal Title: J.Biol.Chem. 282 Pages: 37285-37292
  • Peer Reviewed
• [Journal Article] HSF1 opens chromatin structure of IL-6 promoter to facilitate binding of an activator or a repressor. (2007)
  • Author(s): S. Inouye, et. al.
  • Journal Title: J.Biol.Chem. 282 Pages: 33210-33217
  • Peer Reviewed
• [Journal Article] Genetic evidence for a protective role for heat shock factor 1 and heat shock protein 70 against colitis. (2007)
  • Author(s): K. Tanake, et. al.
  • Journal Title: J.Biol.Chem. 282 Pages: 23240-23252
  • Peer Reviewed
• [Journal Article] Association of heat shock protein 70 induction and the amelioration of experimental autoimmune uveoretinitis mice. (2007)
  • Author(s): H. Kitamei, et. al.
  • Journal Title: Immunobiology 212 Pages: 11-18
  • Peer Reviewed
• [Journal Article] Genetic evidence for a protective role of heat shock factor 1 against irritant-induced gastric lesions. (2007)
  • Author(s): K. Tanaka, et. al.
  • Journal Title: Mol.Pharmacol. 71 Pages: 985-993
  • Peer Reviewed
• [Journal Article] The induction mechanism of the molecular chaperone HSP70 in the gastric mucosa by Geranylgeranylacetone(HSP-inducer). (2007)
  • Author(s): M. Otaka, et. al.
  • Journal Title: Biochem.Biophy.Res.Commun. 353 Pages: 399-404
  • Peer Reviewed
• [Journal Article] HSF1 and constitutively active HSF1 improve vascular endothelial function(heat shock proteins improve vascular endothelial function) (2007)
  • Author(s): T. Uchiyama, et. al.
  • Journal Title: Atherosclerosis 190 Pages: 321-329
  • Peer Reviewed
• [Presentation] 熱ショック転写因子HSF1による発熱・炎症反応の抑制的制御 (2009)
  • Author(s): 井上幸江、滝井良祐、藤本充章、林田直樹、市川仁、中井彰
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] HSF1による新しい蛋白質ホメオスターシスの維持機 (2009)
  • Author(s): 林田直樹、藤本充章、王倍倍、大島功司、新川豊英、市川 仁、井上幸江、瀧井良祐、中井彰
  • Organizer: 09'遺伝情報DECODE・冬のワークショップ
  • Place of Presentation: 越後湯沢(口演)
• [Presentation] Coordinate regulation of heat shock and inflammatory responses by HSF1 (2008)
  • Author(s): A. Nakai
  • Organizer: 6^<th> International Workshop on the Molecular Biology of Stress Responses
  • Place of Presentation: Bangkok,Thailand
  • Year and Date: 2008-03-27
• [Presentation] レンズ発生過程におけるHSF群による転写制御の機構 (2008)
  • Author(s): 藤本 充章, 等
  • Organizer: 08'遺伝情報DECODE・冬のワークショップ
  • Place of Presentation: 新潟越後湯沢
  • Year and Date: 2008-01-22
• [Presentation] Adverse effects of HSF1 activation during feral brain development (2008)
  • Author(s): K.Hashimoto-Torii, M.Torii, X.Liu, M.Fujimoto, A.Nakai, and P.Rakic
  • Organizer: 第31回分子生物学会・第81回日本生化学会
  • Place of Presentation: 神戸
• [Presentation] 遺伝性白内障と関連した熱ショック転写因子HSF4変異体の解析 (2008)
  • Author(s): 大島功司、藤本充章、永瀬隆、林田直樹、瀧井良祐、中井彰
  • Organizer: 第31回日本分子生物学会大会・第81回日本生化学学会
  • Place of Presentation: 神戸
• [Presentation] 熱ショック転写因子HSF1の新たなターゲット遺伝子群による蛋白質ホメオスターシスの調節 (2008)
  • Author(s): 林田直樹、藤本充章、王倍倍、大島功司、新川豊英、市川 仁、井上幸江、瀧井良祐、中井彰
  • Organizer: 第31回日本分子生物学会大会・第81回日本生化学学会
  • Place of Presentation: 神戸
• [Presentation] 温熱ストレスによる炎症性サイトカイン発現の抑制機構 (2008)
  • Author(s): 瀧井良祐、井上幸江、藤本充章、大島功司、王倍倍、新川豊英、市川仁、林田直樹、中井彰
  • Organizer: 第31回日本分子生物学会大会・第81回日本生化学学会
  • Place of Presentation: 神戸
• [Presentation] 熱ショック転写因子HSF4の発生過程と熱ショック応答での役割 (2008)
  • Author(s): 藤本充章、大島功司、新川豊英、王倍倍、林田直樹、瀧井良祐、井上幸江、中井彰
  • Organizer: 第31回日本分子生物学会大会・第81回日本生化学学会
  • Place of Presentation: 神戸
• [Presentation] Analysis of products of HSF4 genes mutated in patients of hereditary cataract (2008)
  • Author(s): K.Ohshima, M.Fujimoto, T.Nagase, T.Shinkawa, B.B.Oh, H.Naoki, R.Takii, and A.Nakai
  • Organizer: Jacques Monod Conference; New ideas for an old family : Heat Shock Factors at crossroads between stress, epigenetics and development
  • Place of Presentation: Roscoff, France
• [Presentation] Mouse HSF3 can protect cells against detrimental stresses (2008)
  • Author(s): M.Fujimoto, T.Katoh, H.Naoki, R.Takii, I.Ohshima, T.Shinkawa, B.B.Oh, S.Inouye, and A.Nakai
  • Organizer: Jacques Monod Conference; New ideas for an old family : Heat Shock Factors at crossroads between stress, epigenetics and development
  • Place of Presentation: Roscoff, France
• [Presentation] HSF interplay during sensory placode development (2008)
  • Author(s): A. Nakai
  • Organizer: Jacques Monod Conference; New ideas for an old family : Heat Shock Factors at crossroads between stress, epigenetics and development
  • Place of Presentation: Roscoff, France
• [Presentation] 熱ショック応答と免疫・炎症反応の協調制御 (2008)
  • Author(s): 中井彰
  • Organizer: 第25回日本ハイパーサーミア学会
  • Place of Presentation: 名古屋
• [Presentation] 熱ショック転写因子によるレンズの恒常性維持機構 (2008)
  • Author(s): 藤本充章、大島功、新川豊英、王倍倍、井上幸江、林田直樹、瀧井良介、中井彰
  • Organizer: 大学共同利用機関法人・自然科学研究機構(生理学研究所)研究会「上皮膜輸送制御の分子機構 : 体内環境恒常性維持機構解明を目指して」
  • Place of Presentation: 岡崎
• [Presentation] Coordinate regulation of heat shock and inflammatory responses by HSF1 (2008)
  • Author(s): A. Nakai
  • Organizer: 6th International Workshop on the Molecular Biology of Stress Responses
  • Place of Presentation: Bangkok, Thailand
• [Presentation] レンズ発生過程におけるHSF群による転写制御の機構08' (2008)
  • Author(s): 藤本充章、大島功司、新川豊英、王倍倍、林田直樹、井上幸江、中井彰
  • Organizer: 遺伝情報DECODE・冬のワークショップ
  • Place of Presentation: 越後湯沢
• [Presentation] HSF interplay during sensory placode development (2008)
  • Author(s): A. Nakai
  • Organizer: Jacques Monod Conference
  • Place of Presentation: Roscoff, France
• [Presentation] Mouse HSF3 can protect cells against detrimental stresses. (2008)
  • Author(s): M. Fujimoto, et. al
  • Organizer: Jacques Monod Conference
  • Place of Presentation: Roscoff, France
• [Presentation] Analysis of products of HSF4 genes mutated in patients of hereditary cataract (2008)
  • Author(s): K. Ohshima, et. al
  • Organizer: Jacques Monod Conference
  • Place of Presentation: Roscoff, France
• [Presentation] ゲノムと遺伝情報・転写とその制御2 (2008)
  • Author(s): 中井 彰
  • Organizer: 第31回日本分子生物学会大会・第81回日本生化学会
  • Place of Presentation: 神戸
• [Presentation] 熱ショック転写因子HSF4の発生過程と熱ショック応答での役割 (2008)
  • Author(s): 藤本充章, 他
  • Organizer: 第31回日本分子生物学会大会・第81回日本生化学会
  • Place of Presentation: 神戸
• [Presentation] 温熱ストレスによる炎症性サイトカイン発現の制御機構 (2008)
  • Author(s): 瀧井良祐, 他
  • Organizer: 第31回日本分子生物学会大会・第81回日本生化学会
  • Place of Presentation: 神戸
• [Presentation] 熱ショック転写因子HSF1の新たなターゲット遺伝子群による蛋白質ホメオスターシスの調節 (2008)
  • Author(s): 林田直樹, 他
  • Organizer: 第31回日本分子生物学会大会・第81回日本生化学会
  • Place of Presentation: 神戸
• [Presentation] 遺伝性白内障と関連した熱ショック転写因子HSF4変異体の解析 (2008)
  • Author(s): 大島功司, 他
  • Organizer: 第31回日本分子生物学会大会・第81回日本生化学会
  • Place of Presentation: 神戸
• [Presentation] Adverse effects of HSF1 activation during feral brain development (2008)
  • Author(s): K. Hashimoto-Torii, et. al
  • Organizer: 第31回日本分子生物学会大会・第81回日本生化学会
  • Place of Presentation: 神戸
• [Presentation] 熱ショック転写因子HSF4が認識するDNA結合配列の同定 (2007)
  • Author(s): 藤本 充章, 等
  • Organizer: 第80回日本生化学会大会・第30回日本分子生物学会年会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] 熱ショック転写因子による細胞の生と死の決定の機構 (2007)
  • Author(s): 林田 直樹, 等
  • Organizer: 大学共同利用機関法人・自然科学研究機構(生理学研究所)研究会
  • Place of Presentation: 岡崎
  • Year and Date: 2007-11-01
• [Presentation] Characterization of the DNA-binding sites of HSF4 that constitutively forms a timer (2007)
  • Author(s): M. Fujimoto, et. al.
  • Organizer: Third international Congress on Stress Responses in Biology and Medicine
  • Place of Presentation: Budapest, Hangary
  • Year and Date: 2007-09-25
• [Presentation] Roles of HSF1 in inflammatory and immune response (2007)
  • Author(s): A. Nakai
  • Organizer: Third international Congress on Stress Responses in Biology and medicine
  • Place of Presentation: Budapest, Hangary
  • Year and Date: 2007-09-24
• [Presentation] 熱ショック転写因子群による恒常性の維持 (2007)
  • Author(s): 中井彰
  • Organizer: GGA-HSP勉強会
  • Place of Presentation: 東京
  • Year and Date: 2007-09-08
• [Presentation] HSF1 plays a role in feedback regulation of the febrile response (2007)
  • Author(s): A. Nakai
  • Organizer: Gordon Research Conference
  • Place of Presentation: Oxford, UK
  • Year and Date: 2007-08-19
• [Presentation] 熱ショック転写因子HSF1のターゲット遺伝子の網羅的解析 (2007)
  • Author(s): 林田直樹、藤本充章、王倍倍、市川仁、井上幸江、中井彰
  • Organizer: 第80回日本生化学会大会・第30回日本分子生物学会年会合同大会
  • Place of Presentation: 横浜
• [Presentation] 熱ショック転写因子HSF4が認識するDNA 結合配列の同定 (2007)
  • Author(s): 藤本充章、大島功司、林田直樹、井上幸江、中井彰
  • Organizer: 第80回日本生化学会大会・第30回日本分子生物学会年会合同大会
  • Place of Presentation: 横浜
• [Presentation] 熱ショック転写因子HSF1はIL-6遺伝子のクロマチンを開くことによって転写制御に関与する (2007)
  • Author(s): 井上幸江、藤本充章、高木栄一、林田直樹、中井彰
  • Organizer: 第80回日本生化学会大会・第30回日本分子生物学会年会合同大会
  • Place of Presentation: 横浜
• [Presentation] 熱ショック転写因子による細胞の生と死の決定の機構大学共同利用機関法人 (2007)
  • Author(s): 林田直樹、藤本充章、高木栄一、大島功、王倍倍、井上幸江、中井彰
  • Organizer: 自然科学研究機構(生理学研究所)研究会「上皮膜機能活性化物質と上皮膜防御の最前線」
  • Place of Presentation: 岡崎
• [Presentation] 熱ショック転写因子群の生理機能 (2007)
  • Author(s): 中井彰
  • Organizer: 第11回Molecular Cardiovascular Conference
  • Place of Presentation: 北海道余市
• [Presentation] Characterization of the DNA-binding sites of HSF4 that constitutively forms a timer (2007)
  • Author(s): M.Fujimoto, E.Takaki, N.Hayashida, S.Inouye, and A.Nakai
  • Organizer: Third International Congress on Stress Responses in Biology and Medicine
  • Place of Presentation: Budapest, Hangary(ポスター)
• [Presentation] Roles of HSF1 in inflammatory and immune response (2007)
  • Author(s): A. Nakai
  • Organizer: Third International Congress on Stress Responses in Biology and Medicine
  • Place of Presentation: Budapest, Hangary
• [Presentation] HSF1 plays a role in feedback regulation of the febrile response (2007)
  • Author(s): A. Nakai
  • Organizer: Gordon Research Conference on "Stress Proteins in Growth, Development & Disease"
  • Place of Presentation: Oxford, UK
• [Book] キーワード : タンパク質の一生蛋白質酵素核酸 (2008)
  • Author(s): 藤本充章、中井彰
  • Total Pages: 978
  • Publisher: 共立出版
• [Book] 実験医学 (2007)
  • Author(s): 中井彰、藤本充章、井上幸江
  • Publisher: 熱ショック転写因子HSF と高次生命現象(25(10))
• [Remarks]
  • URL: http://ds22.cc.yamaguchi-u.ac.jp/~seika2/
• [Remarks]
  • URL: http://ds22.cc.yamaguchi-u.ac.jp/~seika2/