| Project/Area Number |
14571243
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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 |
Digestive surgery
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| Research Institution | Kansai Medical University |
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Principal Investigator |
KAMIYAMA Yasuo Kansai Medical University, Department of Surgery, Professor, 医学部, 教授 (90127069)
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| Co-Investigator(Kenkyū-buntansha) |
KWON A-hon Kansai Medical University, Department of Surgery, Assistant professor, 医学部, 助教授 (70225605)
KAIBORI Masaki Kansai Medical University, Department of Surgery, Reseach associate, 医学部, 助手 (30333199)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | FK506 / Cyclosporin A / Inducible nitric oxide synthase / Interleukin 1 / Nuclear factor-kappa B / Rat cultured hepatocytes / cytokine-induced neutrophil chemoattractant / ラット初代肝細胞培養 / 低酸素障害 / ケトン体比 / Heat shock protein |
|---|
| Research Abstract |
Studies were performed to determine whether the immunosuppressants FK506 and cyclosporin A directly influence gene expression of inducible nitric oxide synthase by IL-1β in hepatocytes. Methods : Primary cultures of rat hepatocytes were treated with IL-1β in the presence and absence of FK506 or cyclosporin A. Release of nitrite into culture medium, levels of inducible nitric oxide synthase protein and mRNA, and activation of NF-κB were compared with the two drugs. Results : IL-1β increased levels of inducible nitric oxide synthase protein and inducible nitric oxide synthase mRNA, as well as nitric oxide production, in the cultured hepatocytes. NF-κB, an important transcription factor in inducible nitric oxide synthase gene expression in response to inflammation, also appeared in the nuclear fraction of hepatocytes after addition of IL-1β. FK506 markedly inhibited the nitric oxide formation, inducible nitric oxide synthase protein synthesis and inducible nitric oxide synthase mRNA expression induced by IL-1β, but cyclosporin A had no effects. Furthermore, FK506 inhibited NF-κB activation and decreased mRNA levels of the p50/p65 subunits of NF-κB. Conclusions : These results demonstrate that FK506, but not cyclosporin A, inhibits the induction of inducible nitric oxide synthase expression during NF-κB activation
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