NF-κB/IκB信号通路在IL-1β诱导的肾系膜细胞环氧化酶-2表达中的作用

目的:探讨核因子-κB(NF-κB)/IκB信号通路在肾小球系膜细胞环氧化酶-2(COX-2)表达中的作用。方法:放射免疫测定法检测系膜细胞培养上清中PGE₂水平;RT-PCR和Westernblot检测COX-2表达;凝胶电泳迁移率(EMSA)和Westernblot检测肾小球系膜细胞中NF-κB活化、p65亚基核转位以及IκBα和IκBβ的降解。结果:IL-1β显著上调系膜细胞PGE₂释放和COX-2表达,PDTC显著抑制IL-1β诱导的COX-2表达及PGE₂释放;IL-1β诱导系膜细胞NF-κB活化,p65核转位及胞浆内IκBα和IκBβ的降解。结论:IL-1β通过NF-κB/IκB信号转导通路诱导肾小球系膜细胞中COX-2表达。

Expression of cyclooxygenase-2 in IL-1β-stimulated mesangial cells is medicated by NF-κB/IκB signal pathway

AIM: To investigate the role of NF-κB/IκB signal pathway in the regulation of cyclooxygenase-2 (COX-2) expression in human mesangial cells (HMC). METHODS: The PGE₂ concentration in supernatants of HMC was measured by radioimmunoassay. COX-2 mRNA and protein expression were determined by RT-PCR and Western blot. Electrophoretic mobility shift assay (EMSA) and Western blot were used to detect the activity of NF-κB and degradation of IκB. RESULTS: IL-1β significantly upregulated COX-2 expression and PGE₂ production in HMC. Significant up-regulation of NF-κB activation, nuclear translocation of p65 subunit, and degradation of IκB α and IκB β were observed in IL-1β-induced HMC. CONCLUSION: Expression of COX-2 in IL-1β-induced HMC is mediated by NF-κB/IκB signal pathway.