TAK1在胶质细胞iNOS表达中的作用机制

Role of TAK1 Induction of iNOS Expression in Glial Cells

目的:研究探讨中枢胶质细胞在炎症反应过程中,转化生长因子β(TGFβ)-激活性激酶1(TAK1)诱导iNOS表达的作用机制。方法:通过在胶质细胞株中瞬时转染TAK1和它的激活蛋白因子(TAK1-b ind ing prote in1TAB1),或与iNOS启动子报告基因(iNOS-Luc)质粒及NFκB-Luc质粒共转染。结果:TAK1明显激活iNOS的表达活性。而且当使用下游激酶p38 MAPK,JNK和NFκB的抑制剂(SB203580,SP600125和CAPE)后,这些表达活性明显被抑制。结论:在胶质细胞内,TAK1在p38 MAPK,JNK和NFκB信号传导途径介导的iNOS的转录表达活性中起着非常重要的作用。

Objective. This study directly tests the role of TGFβ-activated kinase 1 （ TAK1 ） in the induction of inducible nitric oxide （NO） synthase （iNOS） in glial cells, which represent immune-regulatory cells of the CNS. Methods： By transient transfection assays. Transfection of C-6 glia, with TAK1 along with its activator protein, TAKl-binding protein 1 （TAB1） resulted in a marked stimulation of a co-transfected rat iNOS promoter-reporter construct （iNOS-Luc）. Results： TAKl-induced iNOS-Luc activity was substantially inhibited by pharmacological inhibitors of the known downstream kinases, p38 MAPK and JNK,and NFKB （SB203580, SP620125 and CAPE）, and was almost completely blocked by co-expression of a phosphorylation mutant of IκB. Conclusion： The results of these studies provide evidence for an important role for TAKl-mediated intracellular signaling,via p38 MAPK, JNK and NFκB, in the transcriptional activation of iNOS in glial cells.