The effect of immunosuppressant FK506 on hepatic function of graft

免疫抑制剂FK506对移植物肝功能的影响

基本信息

批准号：
14571243
负责人：
KAMIYAMA Yasuo
金额：
$ 2.18万
依托单位：
Kansai Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571243/
关键词：
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

项目摘要

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

进行研究以确定免疫抑制剂FK506和环孢菌素A是否直接影响肝细胞中IL-1β的诱导型一氧化氮合酶的基因表达。方法：在存在和不存在FK506或环孢菌素的情况下，用IL-1β处理大鼠肝细胞的原代培养物。将亚硝酸盐释放到培养基中，将诱导型一氧化氮合酶蛋白和mRNA水平释放到NF-κB的激活中。结果：IL-1β在培养的肝细胞中增加了诱导型一氧化氮合酶蛋白和诱导型一氧化氮合酶mRNA以及一氧化氮的水平。 NF-κB是诱导一氧化氮合酶基因表达的重要转录因子对炎症的反应，在添加IL-1β后也出现在肝细胞的核分裂中。 FK506显着抑制了一氧化氮的形成，诱导的一氧化氮合酶蛋白合成和可诱导的一氧化氮合酶mRNA由IL-1β诱导的，但环孢菌素A没有影响。此外，FK506抑制了NF-κB激活，并提高了NF-κB的p50/p65亚基的mRNA水平。结论：这些结果表明，FK506（而非环孢菌素A）抑制了NF-κB活化过程中一氧化氮合酶表达的诱导