2003 Fiscal Year Final Research Report Summary
Study of the mechanism of liver ischemia-repeifusion injuiy based on modulation of NF-kB activation by gene transfer technique
| Project/Area Number |
13671235
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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 | Hiroshima University |
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Principal Investigator |
MARUBAYASHI Seiji Hiroshima University, Medical and Dental Hospital, Associate Professor, 医学部・歯学部附属病院, 助教授 (80144814)
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| Co-Investigator(Kenkyū-buntansha) |
TASHIRO Hirotaka Hiroshima University, Medical and Dental Hospital, Research Associate, 医学部・歯学部附属病院, 助手
YAHATA Hiroshi Hiroshima University, Medical and Dental Hospital, Associate Professor, 医学部・歯学部附属病院, 助教授 (10191181)
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| Project Period (FY) |
2001 – 2003
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| Keywords | NF-kB decoy / endotoxin-induced liver injury / liver ischemia-reperfusion / NF-kB / cytokine / TNF-alpha |
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| Research Abstract |
The NF-kB is a ubiquitous transcriptional factor involved in the up-regulation of many inflammatory response. We recently demonstrated that NF-kB activity increased during the hepatic ischemia-reperfusion and endotoxin induced shock liver. The present study was undertaken to determine whether NF-kB decoy could suppress proinflammatory gene up-regulation through inhibition of NF-kB activation in endotoxin shock or acute liver rejection model and increase the survival rate of animals. Treatment with NF-kB decoy injected in the portal vein significantly increased survival rates 24 and 48 hours after lipopolysaccharide injection and suppressed the increase of plasma TNF-alpha activity. NF-kB decoy treatment showed inhibitory effect on hydrogen peroxide induced NF-kB activation in Jurkat cells. in the acute liver rejection model in the rat liver transplantation (donor ; DA rats, recipient ; Lewis rats), treatment with NF-kB decoy in the preservation fluid significantly suppressed expression of inflammatory cytokine mRNA and increased the survival rate of the recipient rats. These results suggest that NF-kB decoy can suppress proinflammatory cytokine up-regulation through inhibition of NF-kB activation and it is a promising new drug for the treatment of endotoxin shock and acute liver rejection.
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