C-reactive protein induces VCAM-1 gene expression through NF-kappaB activation in vascular endothelial cells.
C-reactive protein induces VCAM-1 gene expression through NF-kappaB activation in vascular endothelial cells.
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发表时间：
2006
期刊：
影响因子：
5.3
通讯作者：
Daiji Kawanami;K. Maemura;Norihiko Takeda;T. Harada;T. Nojiri;Tetsuya Saito;I. Manabe;Y. Imai;R. Nagai
中科院分区：
文献类型：
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作者：
Daiji Kawanami;K. Maemura;Norihiko Takeda;T. Harada;T. Nojiri;Tetsuya Saito;I. Manabe;Y. Imai;R. Nagai
最近的研究表明，C反应蛋白(CRP)不仅是心血管事件的预测因子，而且还直接作为血管细胞的促炎刺激因子。在这篇报道中，我们研究了CRP诱导血管细胞黏附分子-1(VCAM-1)的分子机制。CRP诱导的VCAM-1mRNA表达可被蛋白激酶C(PKC)抑制剂、p38丝裂原活化蛋白激酶(MAPK)抑制剂和酪氨酸激酶抑制剂所抑制。此外，核因子kappaB(NF-kappaB)抑制剂巴特内酯可阻断VCAM-1的诱导。此外，CRP还能增强VCAM-1启动子的活性，表明CRP在转录水平诱导VCAM-1mRNA表达。核因子-kappaB结合位点突变导致诱导丧失。最后，电泳迁移率改变分析证实了NF-kappaB的p65亚单位与kappaB结合位点的结合。综上所述，我们的研究结果表明，CRP诱导的VCAM-1是由血管内皮细胞中的PKC、p38MAPK、酪氨酸激酶和依赖于NF-kappaB的信号通路介导的。
Recent studies have shown that C-reactive protein (CRP) is not just a predictor of cardiovascular events but also acts directly as a proinflammatory stimulus in vascular cells. In this report, we studied the molecular mechanisms underlying vascular cellular adhesion molecule-1 (VCAM-1) induction by CRP. CRP-induced VCAM-1 mRNA expression and this induction was inhibited by protein kinase C (PKC) inhibitors, p38 mitogen-activated protein kinase (MAPK) inhibitor, and tyrosine kinase inhibitors. In addition, parthenolide, a nuclear factor kappaB (NF-kappaB) inhibitor, abolished VCAM-1 induction. Moreover, CRP increased VCAM-1 promoter activity, indicating that CRP induces VCAM-1 mRNA expression at the transcriptional level. Mutation of NF-kappaB-binding sites resulted in a loss of induction. Finally, an electrophoretic mobility shift assay confirmed binding of the p65 subunit of NF-kappaB to kappaB-binding sites. Taken together, our findings suggest that VCAM-1 induction by CRP is mediated by PKC, p38MAPK, tyrosine kinase and the NF-kappaB-dependent signaling pathways in vascular endothelial cells.