Receptor and Intracellular Signaling Mechanisms Involved in TNF?-induced Expression of Heme Oxygenase-1 in Endothelial Cells / 医学研究杂志

ABSTRACT

Objective To investigate the receptor involved in the TNF?induced HO-1 expression and the related signal transduction mechanisms in the brain microvessel endothelial cells.Methods TNF? receptor 1(TNFR1)knockout murine brain microvessel endothelial cells(BMVECs)in vitro culture were stimulated respectively by TNF?(5ng/ml).After 24 hours,the level of HO-1 gene mRNA were detected by semi-quantitative RT-PCR,the effect of TNF?on JNK 、ERK or transcription factor AP-1 were analyzed by Western blot,while ERK inhibitor(PD98059)or JNK inhibitor(SP600125)were used.Results Exposure of wild-type BMVECs and TNFR1(p55)knockout BMVECs [BVEC/TNF-RI(-/-)] to TNF?(5ng/ml,24 h)caused a marked increase in HO-1 mRNA expression.Furthermore,TNF? stimulation also lead to the activation of JNK,ERK and the transcription factor AP-1 in the BVEC/TNF-RI(-/-),However,incubation with the JNK inhibitor SP600125 but not the ERK inhibitor PD98095 attenuated the TNF?-induction of HO-1 in the BVEC/TNF-RI(-/-).Conclusions TNFR2 and JNK activation but not TNFR1 might be essential for mediating the TNF?-induction of the HO-1 in the endothelial cells.