| Project/Area Number |
18591415
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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 |
General surgery
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| Research Institution | Kagawa University |
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Principal Investigator |
IZUISHI Kunihiko Kagawa University, FUCULTY OF MEDICINE, 講師 (50325346)
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| Co-Investigator(Kenkyū-buntansha) |
MAETA Hajime KAGAWA UNIVERSITY, VICE PRESIDENT (00075508)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Toll-like receptor-4 / TLR-4 / TNF-alpha / IRAK-M / SOCS-1 / JNK / LPS / Toll-like receptor-4 / TLR-4 / TNF-alpha / IRAK-M / JNK / Toll-like receptpr-4 |
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| Research Abstract |
BACKGROUND: LIVER ISCHEMIA AND REPERFUSION-INDUCED TISSUE INJURY INVOLVE A ROBUST INFLAMMATORY RESPONSE, BUT THE PROXIMAL EVENTS IN REPERFUSION INJURY REMAIN INCOMPLETELY DEFINED. TOLL-LIKE RECEPTOR 4 (TLR4) IS A PROXIMAL SIGNALING RECEPTOR IN INNATE IMMUNE RESPONSES TO LIPOPOLYSACCHARIDE. THIS STUDY ASSESSED THE ROLE OF TLR4 IN LIVER ISCHEMIA REPERFUSION INJURY IN A MURINE MODEL. METHODS AND RESULTS: LIVER ISCHEMIA-REPERFUSION WAS PERFORMED ON TLR4-DEFICIENT MICE AND CONTROLS. MICE WERE SUBJECTED TO 60-90 MIN ISCHEMIA AND THEN REPERFUSED. TLR4-DEFICIENT MICE DECREASED NECROTIC AREA SIGNIFICANTLY THAN CONTROL MICE HISTOLOGICALLY. INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE-1(IRAK-1), THE DOWN STREAM PATHWAY OF TLR4, WAS STRONGLY PHOSPHORYLATED AFTER REPERFUSION. THE PRETREATMENT OF LIPOPOLYSACCHARIDE SHOWED THE PROTECTIVE EFFECT AGAINST ISCHEMIA REPERFUSION INJURY. THIS PROTECTIVE EFFECT WAS CAUSED BY QUICK INDUCTION OF SOCS-1, FEEDBACK INHIBITOR OF TLR4 PATHWAY, AFTER ISCHEMIA. CONCLUSIONS: TLR4-DEFICIENT MICE SUSTAIN SMALLER NECROSIS AND EXHIBIT LESS INFLAMMATION AFTER LIVER ISCHEMIA-REPERFUSION INJURY. OUR DATA SUGGEST THAT THE NEGATIVE FEEDBACK INHIBITOR, SOCS-1, PLAYED AN IMPORTANT ROLE OF TOLERANCE FOR ISCHEMIA REPERFUSION INJURY.
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