Establishment of a new experimental model for human septic shock

• Project/Area Number: 19590461
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Aichi Medical University
• Principal Investigator: YOKOCHI Takashi Aichi Medical University, 医学部, 教授 (20126915)
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: エンドトキシン / ガラクトシルセラミド / NKT細胞 / インターフェロン / LPS / 腫瘍懐死因子 / 血管透過性 / エンドトキシンショック / 腫瘍壊死因子 / VCAM-1 / VLA4細胞

Research Abstract

ガラクトシルセラミド(α-GalCer)を投与すると肺のNKT細胞が活性化し、肺局所でγ-インターフェロンが産生され、各種接着因子が発現され、炎症性細胞が肺に集積する。これがエンドトキシン投与による肺病変の準備段階となる。それら炎症性細胞をエンドトキシンが刺激して、各種炎症性メディエーターを過剰に産生させ、血管内皮や肺胞上皮などの障害が起こり、血管透過性を亢進し、肺病変、呼吸不全を導き、致死的ショックを誘導することを明らかにした。

Research Products

• [Journal Article] Concanavalin A induces formation of osteoclast-like cells in RAW 264.7 mouse macrophage cells (2009)
  • Author(s): Kasugai C, Morikawa A, Naiki Y, Koide N, Komatsu T, Yoshida T, Yokochi T.
  • Journal Title: Immunopharmacol Immunotoxicol 2008 31 Pages: 103-7
• [Journal Article] Lipopolysaccharide augments the in vivo lethal action of doxorubicin against mice via hepatic damage (2008)
  • Author(s): Hassan F, Morikawa A, Islam S, Tumurkhuu G, Dagvadorj J, Koide N, Naiki Y, Mori I, Yoshida T, Yokochi T.
  • Journal Title: Clin Exp Immunol 151 Pages: 334-40
• [Journal Article] The mechanism of development of acute lung injury in lethal endotoxic shock using alpha-galactosylceramide (alpha-GalCer) sensitization (2008)
  • Author(s): Tumurkhuu G, Koide N, Dagvadorj J, Morikawa A, Hassan F, Islam S, Naiki Y, Mori I, Yoshida T, Yokochi T.
  • Journal Title: Clin Exp Immunol 152 Pages: 182-91
• [Journal Article] Role of V{alpha}14+ NKT cells in the development of Hepatitis B virus-specific CTL : activation of V{alpha}14+ NKT cells promotes the breakage of CTL tolerance (2008)
  • Author(s): Ito H, Ando K, Ishikawa T, Nakayama T, Taniguchi M, Saito K, Imawari M, Moriwaki H, Yokochi T, Kakumu S, Seishima M.
  • Journal Title: Int Immunol 20 Pages: 869-79
• [Journal Article] Interleukin-10 inhibits tumor necrosis factor-alpha production in lipopolysaccharide -stimulated RAW 264.7 cells through reduced MyD88 expression (2008)
  • Author(s): Dagvadorj J, Naiki Y, Tumurkhuu G, Hassan F, Islam S, Koide N, Mori I, Yoshida T, Yokochi T.
  • Journal Title: Innate Immun 14 Pages: 109-15
• [Journal Article] Hydrogen peroxide induces the production of tumor necrosis factor-{alpha} in RAW 264.7 macrophage cells via activation of p38 and stress-activated protein kinase (2008)
  • Author(s): Nakao N, Kurokawa T, Nonami T, Tumurkhuu G, Koide N, Yokochi T.
  • Journal Title: Innate Immun 14 Pages: 190-6
• [Journal Article] Thalidomide inhibits epidermal growth factor-induced cell growth in mouse and human monocytic leukemia cells via Ras inactivation (2008)
  • Author(s): Noman AS, Koide N, Khuda II, Dagvadorj J, Tumurkhuu G, Naiki Y, Komatsu T, Yoshida T, Yokochi T.
  • Journal Title: Biochem Biophys Res Commun 374 Pages: 683-7
• [Journal Article] Lipopolysaccharide augments the in vivo lethal action of doxorubiein against mice via hepatic damage (2008)
  • Author(s): Hass an F., et al.
  • Journal Title: Clin Exp Immunol 151 Pages: 334-340
  • Peer Reviewed
• [Journal Article] The mechanism of development of acute lung injury in lethal endotoxic shock using alpha-galactosylcerramide (alpa-GalCer) sensitization (2008)
  • Author(s): Tumurkhuu G., et al.
  • Journal Title: Clin Exp Immunol 152 Pages: 182-192
  • Peer Reviewed
• [Journal Article] Role of Valpha14+NKT cells in the development of hepati tis Bvirus-specific CTL : activation of valpha14+NKT cells promotes the breakage of CTL tolerance (2008)
  • Author(s): Ito H., et al.
  • Journal Title: Int Immunol 20 Pages: 869-879
  • Peer Reviewed
• [Journal Article] Thalidomide inhibits epidermal growth factor-induced cell growth in mouse and human monocytic leukemia cells via Ras inactivation (2008)
  • Author(s): Noman AS, et al.
  • Journal Title: Biochem Biophys Res Commun 374 Pages: 683-687
  • Peer Reviewed
• [Journal Article] Interleukin-10 inhibits tumor necrosis factor-alpha pro duetion in lipopolysaccharide-stimulated RAW 264.7 cells through reduced MyD88 expression (2008)
  • Author(s): Dagvadorj J., et al.
  • Journal Title: Innate Immun 14 Pages: 109-115
  • Peer Reviewed
• [Journal Article] Hydrogen peroxide induces the production of tumor necrosis factor-{alpha} in RAW 264.7 macrophage cells via a ctivation of p38 and stress-activated protein kinase (2008)
  • Author(s): Nakao N., et al.
  • Journal Title: Innate Immune 14 Pages: 190-196
  • Peer Reviewed
• [Journal Article] The mechanism of development of acute lung injury inl ethal endotoxic shock using alpha-galactosylceramide(alpha-Ga1Cer)sensitization (2008)
  • Author(s): Tumurkhuu G, et. al.
  • Journal Title: Clin Exp Immunol. 152 Pages: 182-191
  • Peer Reviewed
• [Journal Article] MnTBAP, a synthetic metalloporphyrin, inhibits production of tumor necrosis factor-alpha in lipopolysaccharide-stimulated RAW 264.7 macrophages cells via inhibiting oxidative stress-mediating p38 and SAPK/JNK signaling (2007)
  • Author(s): Tumurkhuu G, Koide N, Dagvadorj J, Hassan F, Islam S, Naiki Y, Mori I, Yoshida T, Yokochi T.
  • Journal Title: FEMS Immunol Med Microbiol 49 Pages: 304-11
• [Journal Article] Bacterial lipopolysaccharide induces osteoclast formation in RAW 264.7 macrophage cells (2007)
  • Author(s): Islam S, Hassan F, Tumurkhuu G, Dagvadorj J, Koide N, Naiki Y, Mori I, Yoshida T, Yokochi T.
  • Journal Title: Biochem Biophys Res Commun 360 Pages: 346-51
• [Journal Article] Lipopolysaccharide and interferon-gamma enhance Fas-mediated cell death in mouse vascular endothelial cells via augmentation of Fas expression (2007)
  • Author(s): Koide N, Morikawa A, Tumurkhuu G, Dagvadorj J, Hassan F, Islam S, Naiki Y, Mori I, Yoshida T, Yokochi T.
  • Journal Title: Clin Exp Immunol 150 Pages: 553-60
• [Journal Article] Lipopolysaccharide augments the in vivo lethal action of doxorubicin against mice via hepatic damage (2007)
  • Author(s): Hassan F., et. al.
  • Journal Title: Clin Exp Immunol. 151 Pages: 334-340
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide and interferon-gamma enhance Fas-mediated cell death in mouse vascular endothelial cells via augmentation of Fas expression (2007)
  • Author(s): Koide N., et. al.
  • Journal Title: Clin Exp Immunol. 150 Pages: 553-560
  • Peer Reviewed
• [Presentation] IL-10 prevents LPS induced IL-6 production via inhibition of IkappaB-zeta by Bcl-3 (2009)
  • Author(s): Dagvadorj J, et. al.
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-03-13
• [Presentation] IL-10 prevebnts LPS induced IL-6 production via inhibition of IkappaB-zeta by Bcl-3 (2009)
  • Author(s): Dagvadorj J
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-03-13
• [Presentation] Mechanism of acute lung injury in lethal endotoxic shock using alpha-galactosylceramide (2008)
  • Author(s): Tumurkhuu G, et. al.
  • Organizer: 日本細菌学会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2008-03-24