| Project/Area Number |
17591888
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | Okayama University |
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Principal Investigator |
KATAYAMA Hiroshi Okayama University, Hospitals, Associate Professor (90161067)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Toru Okayama University, Hospitals, SiniorAssistant Professor (40252952)
MORITA Kiyoshi Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor (40108171)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,960,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Sepsis / Inflammation / Oxidative, stress / Interleukin-11 / Heme oxygenase-1 / Hepatic, injury / Carbon, tetrachloride / Heme / 出血性ショック / 急性肺傷害 / ウリナスタチン / TNF-α / iNOS / 敗血症 / MODS / インターロイキン-11 / tumor necrosis factor alpha / Heme Oxygenase-1 / 肝臓 / tumor necrosis factor-alpha / NF-kappaB |
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| Research Abstract |
Excessive systemic inflammatory responses in sepsis cause severe tissue injuries leading to multiple organ failures including that of liver, the target organ as well as a source of inflammatory mediators in sepsis. Interleukin-11 (IL-11) is a pleiotropic cytokine that can suppress inflammation through the down-regulation of multiple pro-inflammatory mediators. We previously reported that treatment of rats with IL-11 ameliorated hepatic injury in a rat model of endotoxemia by its anti-inflammatory property. However, the precise mechanism behind the anti-inflammatory effect of IL-11 is unclear and yet be determined. Recently, it has been reported that treatment of cultured hepatocytes with IL-11 induces heme oxygenase-1 (HO-1) in vitro. HO-1, the rate-limiting enzyme in heme catabolism, is induced by oxidative stress and is thought to confer protection against oxidative tissue injuries. Thus, in the present research project, we administered IL-11 to a rat model of acute liver failure produced by intraperitoneal injection of carbon tetrachloride (CCI_4) and examined its effect on hepatic injury and inflammation. We found that IL-11 treatment of rats induces both HO-1 mRNA and its protein highly specifically in the liver. IL-11 treatment also markedly ameliorated CCI_4-induced oxidative hepatic injury and inflammation. In contrast, administration of tin-mesoporphyrin (SnMP), a specific competitive inhibitor of HO activity, to IL-11-treated animals completely abolished the cytoprotective effect of IL-11. Our findings thus indicate that treatment with IL-11 highly protective against the CCl_4-induced hepatic injury by virtue of its ability to induce HO-1 in the liver. Induction of hepatic HO-1 by IL-11 treatment thus may be a useful therapeutic means against oxidative liver injuries, including CCl_4 intoxication.
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