2004 Fiscal Year Final Research Report Summary
The effect of immunosuppressant FK506 on hepatic function of graft
| Project/Area Number |
14571243
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | Kansai Medical University |
|---|
Principal Investigator |
KAMIYAMA Yasuo Kansai Medical University, Department of Surgery, Professor, 医学部, 教授 (90127069)
|
|---|
| 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)
|
|---|
| Project Period (FY) |
2002 – 2004
|
| Keywords | FK506 / Cyclosporin A / Inducible nitric oxide synthase / Interleukin 1 / Nuclear factor-kappa B / Rat cultured hepatocytes |
|---|
| 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
|
