The role of transcription factor IRF-3 in cardiac disease

• Project/Area Number: 19590492
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The University of Tokyo
• Principal Investigator: YANAI Hideyuki The University of Tokyo, 大学院・医学系研究科, 助教 (70431765)
• Co-Investigator(Kenkyū-buntansha): TSUSHIMA Kensuke 東京大学, 大学院・医学系研究科, 助教 (50436482)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 心疾患 / IRF / アンギオテンシン / TLR / サイトカイン

Research Abstract

心肥大病態モデルマウスに昇圧剤アンジオテンシン(Ang)IIを投与すると、野生型マウスでは高血圧性心疾患に見られる心臓の線維化が進行するがIRF(IFN regulatory factor)ファミリー遺伝子Irf3欠損マウスでは線維化が起きない事、また骨髄系由来細胞のIRF3がAngII 下流でセリン残基リン酸化を受け活性化し、線維化に関与する事を見いだした。
さらにDNAマイクロアレイ解析によりAngII-IRF3 経路のケモカイン・心疾患関連遺伝子誘導への関与を明らかとした。

Research Products

• [Journal Article] Regulation of the cytosolic DNA-sensingsystem in innate immunity : a current view (2009)
  • Author(s): Yanai H, Savitsky D, Tamura T, Taniguchi T.
  • Journal Title: Curr Opin Immunol 1 Pages: 17-22
  • Peer Reviewed
• [Journal Article] Critical role for constitutive type Iinterferon signaling in the prevention ofcellular transformation (2009)
  • Author(s): Chen HM, Tanaka N, Mitani Y, Oda E,Nozawa H, Chen JZ, Yanai H, Negishi H, ChoiMK, Iwasaki T, Yamamoto H, Taniguchi T, Takaoka A.
  • Journal Title: Cancer Sci 100 Pages: 449-456
  • Peer Reviewed
• [Journal Article] Regulation of the cytosolic DNA-sensing system in innate immunity: a currentView. (2009)
  • Author(s): Yanai H. et al.
  • Journal Title: Current Opmin in Immunology 21 Pages: 17-22
  • Peer Reviewed
• [Journal Article] Regulation ofinnate immune responses by DAI(DLM-1/ZBP1) and other DNA-sensingmolecules (2008)
  • Author(s): Wang Z., Choi MK., Ban T., Yanai H., Negishi H., Lu Y., Tamura T., Takaoka A., Nishikura K. and Taniguchi T.
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 5477-5482
  • Peer Reviewed
• [Journal Article] Acritical link between Toll-like receptor 3 andtype II interferon signaling pathways inantiviral innate immunity (2008)
  • Author(s): Negishi H, Osawa T, Ogami K, Ouyang X, Sakaguchi S, Koshiba R, Yanai H, Seko Y, Shitara H, Bishop K, Yonekawa H, Tamura T,Kaisho T, Taya C, Taniguchi T, Honda K.
  • Journal Title: Proc Natl Acad Sci USA 105 Pages: 20446-20451
  • Peer Reviewed
• [Journal Article] A cell-type-specificrequirement for IFN regulatory factor 5(IRF5) in Fas-induced apoptosis (2008)
  • Author(s): Couzinet A., Tamura K., Chen HM.,Nishimura K., Wang Z., Morishita Y., Takeda K., Yagita H., Yanai H., Taniguchi T. and Tamura T.
  • Journal Title: Proc. Natl.Acad. Sci. U.S.A. 105 Pages: 2556-2561
  • Peer Reviewed
• [Journal Article] The IRF family transcriptionfactors in immunity and oncogenesis (2008)
  • Author(s): Tamura T., Yanai H., Savitsky D. and Taniguchi T.
  • Journal Title: Annu.Rev. Immunol 26 Pages: 535-584
  • Peer Reviewed
• [Journal Article] IRF ファミリー転写因子と生体防御シグナル (2008)
  • Author(s): 柳井秀元・谷口維紹
  • Journal Title: 蛋白質核酸酵素(共立出版) 53 Pages: 1231-1238
• [Journal Article] Critical role for constitutive type I interferon signaling in the prevention of cellular transformation. (2008)
  • Author(s): Chen HM. et al.
  • Journal Title: Cancer Science 100 Pages: 449-456
  • Peer Reviewed
• [Journal Article] A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity (2008)
  • Author(s): Negishi H. et al.
  • Journal Title: Proceedings of National Academy of Science USA 105 Pages: 20446-20451
  • Peer Reviewed
• [Journal Article] A cell-type-specific requirement for IFN regulatory factor 5 (IRFS) in Fas-induced apoptosis. (2008)
  • Author(s): Couzinet A., et. al.
  • Journal Title: Proceedings of National Academy of Science USA 105 Pages: 2556-2561
  • Peer Reviewed
• [Journal Article] The IRF Family Transcription Factors in Immunity and Oncogenesis. (2008)
  • Author(s): Tamura T., et. al.
  • Journal Title: Annual Review of Immunology 26 Pages: 535-584
  • Peer Reviewed
• [Journal Article] Regulation of innate immune responses by DAI(DLM-1/ZBP1) and other DNA-sensing molecules. (2008)
  • Author(s): Wang Z., et. al.
  • Journal Title: Proceedings of National Academy of Science USA 105 Pages: 5477-5482
  • Peer Reviewed
• [Journal Article] Effects of hydrophobic amino acidsubstitution in Pleurotus ostreatusproteinase A inhibitor 1 on its structure andfunctions as protease inhibitor andintramolecular chaperone (2007)
  • Author(s): Kojima S., Iwahara A., Hisano Y. and Yanai H.
  • Journal Title: Protein Eng. Des. Sel 103 Pages: 211-217
  • Peer Reviewed
• [Journal Article] Role of IFN regulatory factor 5 transcription factor in antiviral immunityand tumor suppression. Proc (2007)
  • Author(s): Yanai H., Chen HM., Inuzuka T., Kondo S.,Mak TW., Takaoka A., Honda K. and Taniguchi T.
  • Journal Title: Natl. Acad. Sci.USA 104 Pages: 3402-3407
  • Peer Reviewed
• [Journal Article] DAI (DLM-1/ZBP1) is acytosolic DNA sensor and an activator ofinnate immune response (2007)
  • Author(s): Takaoka A., Wang A., Choi MK., Yanai H., Negishi H., Ban T., Lu Y., Miyagishi M.,Kodama T., Honda K., Ohba Y. and Taniguchi T.
  • Journal Title: Nature 448 Pages: 501-505
  • Peer Reviewed
• [Journal Article] DAI(DLM-1/ZBP1)is a cytosolic DNA sensor and an activator of innate immune response. (2007)
  • Author(s): Takaoka A., et. al.
  • Journal Title: Nature 448 Pages: 501-505
  • Peer Reviewed
• [Presentation] Regulation of innate immuneresponses by DAI(DLM-1/ZBP1) and other DNA-sensing molecules (2008)
  • Author(s): 柳井秀元
  • Organizer: 第38回日本免疫学会総会・シンポジウム
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2008-12-02
• [Presentation] Regulation of innate immune responses by DAI(DLM-1/ZBP1) and other DNA-sensing molecules (2008)
  • Author(s): 柳井秀元
  • Organizer: 日本免疫学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2008-12-02
• [Presentation] IRF-5の抗ウイルス応答及び抗腫瘍応答における役割 (2007)
  • Author(s): 柳井 秀元
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-04