Epigenetic gene regulation in sepsis

• Project/Area Number: 22790956
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Infectious disease medicine
• Research Institution: Keio University
• Principal Investigator: ISHII Makoto 慶應義塾大学, 医学部, 特任助教 (30317333)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 敗血症 / エピジェネティクス

Research Abstract

We evaluated the epigenetic gene regulation in mice model of polymicrobial sepsis. The peritoneal macrophages recovered from septic mice showed M2 phenotype and was regulated by histone modification. CXCR2 levels in peripheral neutrophils recovered from septic mice were also regulated by epigenetic change, contributing to worsening the severity of sepsis. In addition, we showed the importance of MLL, a histone H3K4 methyltransferase, during sepsis.

Research Products

• [Journal Article] Roles of IL-17 in an experimental Legionella pneumonia model (2012)
  • Author(s): Kimizuka Y, Kimura S, Saga T, Ishii M, Hasegawa N, Betsuyaku T, Iwakura Y, Tateda K, Yamaguchi K
  • Journal Title: Infect Immun Volume: 80 Pages: 1121-1127
  • Peer Reviewed
• [Journal Article] Roles of interleukin-17 in an experimental Legionella pneumophila pneumonia model (2012)
  • Author(s): Kimizuka Y
  • Journal Title: Infection and Immunity Volume: 80 Pages: 1121-1127
  • Peer Reviewed
• [Journal Article] Carbon black nanoparticles enhance bleomycin-induced lung inflammatory and fibrotic changes in mice (2011)
  • Author(s): Kamata H, Tasaka S, Inoue K, Miyamoto K, Nakano Y, Shinoda H, Kimizuka Y, Fujiwara H, Ishii M, Hasegawa N, Takamiya R, Fujishima S, Takano H, Ishizaka A
  • Journal Title: Exp Biol Med Volume: 236 Pages: 315-324
  • Peer Reviewed
• [Journal Article] 特集呼吸器病原体-病原因特集呼吸器病原体-病原因子-生体反応感染症におけるエピジェネティクス (2011)
  • Author(s): 石井誠
  • Journal Title: 呼吸器内科 Volume: 19 Pages: 71-76
• [Journal Article] Carbon black nanoparticles enhance bleomycin-induced lung inflammatory and fibrotic changes in mice (2011)
  • Author(s): Kamata H
  • Journal Title: Experimental Biology and Medicine Volume: 236 Pages: 315-324
  • Peer Reviewed
• [Journal Article] 感染症におけるエピジェネティクス (2011)
  • Author(s): 石井誠
  • Journal Title: 呼吸器内科 Volume: 19 Pages: 71-76
• [Journal Article] Impaired CD4+T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis (2010)
  • Author(s): Carson WF 4th, Cavassani KA, Ito T, Schaller M, Ishii M, Dou Y, Kunkel SL
  • Journal Title: Eur J Immunol Volume: 40 Pages: 998-1010
  • Peer Reviewed
• [Journal Article] The post sepsis-induced expansion and enhanced function of regulatory T cells creates an environment to potentiate tumor growth (2010)
  • Author(s): Cavassani CA, Wen H, Moreira AP, Schaller MA, Carson IV WF, Ishii M, Lindell DM, Lukacs NW, Keshamouni WG, Hogaboam CM, Kunkel SL
  • Journal Title: Blood Volume: 115 Pages: 4403-4411
  • Peer Reviewed
• [Journal Article] 最新ARDSの全てーARDSの疾患感受性遺伝子とエピジェネティック制御-あらたな治療法開発に向けて (2010)
  • Author(s): 石井誠、山口佳寿博
  • Journal Title: 医学のあゆみ別冊ARDSのすべて Pages: 231-236
• [Journal Article] The post sepsis-induced expansion and enhanced function of regulatory T cells creates an environment to potentiate tumor growth. (2010)
  • Author(s): Cavassani CA
  • Journal Title: Blood Volume: 115 Pages: 4403-4411
  • Peer Reviewed
• [Journal Article] Impaired CD4+ T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis. (2010)
  • Author(s): Carson WF 4th
  • Journal Title: European Journal of Immunology Volume: 40 Pages: 998-1010
  • Peer Reviewed
• [Presentation] Prostaglandin D2 Receptor CRTH2 is A Critical Regulator in A Mice Model of Polymicrobial Sepsis (2011)
  • Author(s): Ishii M, Asano K, Namkoong H, Kagawa S, Nakamura M, Hirai H, Nagata K, Tasaka S, Hasegawa N
  • Organizer: The 34th annual conference on shock(American shock society)
  • Place of Presentation: Nor Fork
  • Year and Date: 2011-06-12
• [Presentation] Critical Roles Of Prostaglandin D2 Receptor CRTH2 In A Mice Model Of Polymicrobial Sepsis (2011)
  • Author(s): Ishii M, Hasegawa N, Mizoguchi K, Namkoong H, Kagawa S, Nakamura M, Hirai H, Nagata K, Tasaka S, Asano K
  • Organizer: The 107th annual International Conference of American thoracic society
  • Place of Presentation: Denver
  • Year and Date: 2011-05-16
• [Presentation] Critical Roles Of Prostaglandin D2 Receptor CRTH2 In A Mice Model Of Polymicrobial Sepsis (2011)
  • Author(s): Ishii M
  • Organizer: The 107th annual International Conference of American thoracic society
  • Place of Presentation: Denver (U.S.A.)
  • Year and Date: 2011-05-16
• [Presentation] Mice Haploinsufficient For The Histone Methyltransferase MLL Exhibit Decreased Inflammatory Responses During Polymicrobial Sepsis (2011)
  • Author(s): Carson WF, Cavassani K, Schaller M, Li X, Ishii M, Ito T, Lukacs NW, Hogaboam CM, Dou Y, Kunkel SL
  • Organizer: The 107th annual International Conference of American thoracic society
  • Place of Presentation: Denver
  • Year and Date: 2011-05-15
• [Presentation] Prostaglandin D2 Receptor CRTH2 is A Critical Regulator in A Mice Model of Polymicrobial Sepsis (2011)
  • Author(s): Ishii M, Hasegawa N, Mizoguchi K, Namkoong H, Kagawa S, Nakamura M, Hirai H, Nagata K, Tasaka S, Asano K
  • Organizer: 第51回日本呼吸器学会
  • Place of Presentation: 東京
  • Year and Date: 2011-04-24
• [Presentation] 敗血症におけるプロスタグランジンD2とそのリセプターCRTH2の役割に関する検討 (2010)
  • Author(s): 石井誠、浅野浩一郎、溝口孝輔、鎌田浩史、君塚善文、藤原宏、船津洋平、加川志津子、中村正孝、平井博之、永田欽也、田坂定智、長谷川直樹、石坂彰敏
  • Organizer: 第25回日本Shock学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-29
• [Presentation] 敗血症におけるプロスタグランジンD2とそのリセプターCRTH2の役割に関する検討 (2010)
  • Author(s): 石井誠
  • Organizer: 第25回 日本Shock学会総会
  • Place of Presentation: 東京 砂防会館・シェーンバッハサボー
  • Year and Date: 2010-05-21
• [Presentation] Critical roles of Toll-like receptor 9 on sepsis-induced acute lung injury (2010)
  • Author(s): Ishii M, Hogaboam CM, Ishizaka A, Kunkel SL
  • Organizer: The 106th annual International Conference of American thoracic society
  • Place of Presentation: New Orleans
  • Year and Date: 2010-05-16
• [Presentation] 敗血症性急性肺損傷におけるToll-like receptor 9(TLR9)の役割の検討 (2010)
  • Author(s): 石井誠、石坂彰敏、Steven L. Kunkel
  • Organizer: 第50回日本呼吸器学会
  • Place of Presentation: 京都
  • Year and Date: 2010-04-24