Effects of FK506 on acute allograft rejection in transplanted rat heart: the role of mitogen-activated protein kinases, AP-1 and NF-kappaB.

Abstract

To scrutinize the effect of the immunosuppressant on acute allograft rejection as related to the intracellular signal transduction, heterotopic cardiac transplantation was performed from DA rat to Lewis rat with/without FK506. In the experimental group, recipients were given FK506 intramuscularly for 5 days. The control group received placebo. Allograft survivals were compared between two groups. For the assay of mitogen-activated protein kinase (MAPKs) families, activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) in the left ventricular free wall (LV) and septum (SEP) of the grafts, rats were sacrificed on POD 5 (n=5 in each group). Extracellular signal-regulated kinase (ERK) and p38MAPK were measured using Western blot analysis. AP-1 and NF-kappaB DNA binding activities were measured by electrophoretic mobility shift assay. FK506 prolonged allograft survival (6.5 vs 31 days), and suppressed activation of myocardial MAPKs (ERK: 66% in LV and 67% in SEP, p38MAPK: 62% in LV and 72% in SEP), AP-1 (24% in LV and 18% in SEP), and NF-kappaB (41% in LV and 20% in SEP) (the mean value of activities in the control group was represented as 100%). These results suggest that the signal transduction pathways may play important roles in acute allograft rejection in rat cardiac transplantation.

Cite this paper

@article{Aoyama2003EffectsOF, title={Effects of FK506 on acute allograft rejection in transplanted rat heart: the role of mitogen-activated protein kinases, AP-1 and NF-kappaB.}, author={Takanobu Aoyama and Shigefumi Suehiro and Hidekazu Hirai and Toshihiko Shibata and Minoru Yoshiyama and Takashi Omura and Shokei Kim and Hiroaki Kinoshita}, journal={Osaka city medical journal}, year={2003}, volume={49 1}, pages={1-10} }