NF-κB/IκB信号通路介导血管紧张素Ⅱ诱导的系膜细胞促炎性细胞因子表达

目的：探讨核因子—κB(NF—κB)／IκB信号通路在血管紧张素Ⅱ(AngⅡ)诱导的肾小球系膜细胞促炎性细胞因子表达中的作用。方法：应用核酸酶保护法检测系膜细胞肿瘤坏死因子α(TNF—α)、IL-1α和IL-1β mRNA表达；应用凝胶电泳迁移率和Western blot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：正常培养状态下，系膜细胞可组成型表达TNF—α和IL—1β，而不表达IL-1αmRNA，AngⅡ刺激后促炎性细胞因子表达显著上调，NF—κB特异性抑制剂2-硫代氨基甲酸吡咯烷显著抑制AngⅡ诱导的促炎性细胞因子基因表达；AngⅡ诱导系膜细胞NF—κB活化，p65核转位及胞质内IκBα和IκBα的降解。结论：AngⅡ诱导肾小球系膜细胞中促炎性细胞因子表达可能通过NF—κB／IκB信号转导通路来实现。

NF-κB/IκB Signal Pathway Regulated Ang Ⅱ-induced Proinflammatory Cytokines Synthesis by Human Mesangial Cells

Objective:To investigate the role of NF-KB/lKB signal pathway in the regulation of proinflammatory cytokines in Ang II-induced human mesangial cells (HMC) . Methods: TNF-a, IL-la and IL-lp mRNA expression was determined by ribonuclease protection assay. Electrophoretic mobility shift assay (EMSA) and Western Blot were used to detect the activity of NF-kB and degradation of 1KB. Results: HMC incubated in medium alone did not express IL-la mRNA, but there was constitutive mRNA expression TNFa and IL-1b in unstimulated cells. Ang II significantly upregulated TNF-a, IL-1a and IL-1b mRNA expression. Significant up-regulation of NF-KB activation, nuclear translocation of p65 subunit, and degradation of IkBa and IkBb were observed in Ang II-induced HMC. Conclusions: Expression of proinflammatory cytokines in Ang Il-induce HMC was mediated by NF-KB/lKB signal pathway.