| Project/Area Number |
24659806
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Emergency medicine
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
UCHIYAMA Ryosuke 兵庫医科大学, 医学部, 講師 (20456891)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 劇症肝炎 / Concanavalin A / 微小循環傷害 / 組織因子 / interferon gamma / Tumor necrosis factor / クッパー細胞 / 肝類洞内皮細胞 / Interferon gamma / Tumor Necrosis Factor / 血栓性肝炎 / STAT1 / Kupffer細胞 / 類洞内皮細胞 |
|---|
| Research Abstract |
Concanavalin A (Con A) treatment induces fulminant hepatitis in mice in a manner dependent on interferon (IFN)-gamma. As previously reported, treatment with the anticoagulant heparin protects against Con A hepatitis, despite healthy production of IFN-gamma. Here, we investigated the mechanisms for hypercoagulation-mediated hepatitis. Mice deficient in IFN-gamma were resistant to Con A hepatitis without induction of systemic and hepatic hypercoagulation. This suggests that IFN-gamma is necessary for the thrombus-associated changes. Neutralization of tissue factor, that is essential for the activation of coagulation cascade, resulted in the protection of this hepatitis despited normal induction of IFN-gamma. Responsiveness to IFN-gamma was required for both hepatic macrophages and endothelial cells, which expressed tissue factor after Con A challenge. Thus, proinflammatory signal elicited by IFN-gamma in various liver cells is necessary for the development of Con A hepatitis.
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