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首页> 外文期刊>Cellular Physiology and Biochemistry >Toll-Like Receptor 4 Signaling Mediates Inflammatory Activation Induced by C-Reactive Protein in Vascular Smooth Muscle Cells
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Toll-Like Receptor 4 Signaling Mediates Inflammatory Activation Induced by C-Reactive Protein in Vascular Smooth Muscle Cells

机译:类似Toll的受体4信号介导C反应蛋白在血管平滑肌细胞中诱导的炎症激活。

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C-reactive protein (CRP) is considered to induce the inflammatory response during atherosclerosis. Toll-like receptor 4 (TLR4)-mediated inflammatory signaling has been shown to facilitate atherogenesis. It remains thoroughly unknown whether TLR4 mediates the proinflammatory effect of CRP. Thus, the study was designed to explore TLR4-related mechanism of proinflammatory effect of CRP in rat vascular smooth muscle cells (VSMCs). CRP increased mRNA levels and protein expressions of vascular endothelial growth factor A (VEGF-A) and inducible nitric oxide synthase (iNOS) in VSMCs, and enhanced NO secretion in the medium. But, CRP hindered nuclear translocation of glucocorticoid receptor (GR) and decreased mRNA level and protein phosphorylation of GR in VSMCs. TLR4 small-interfering RNA (siRNA) significantly reversed the effects of CRP. These suggest that CRP is able to induce inflammatory responses via TLR4 in VSMCs. More importantly, our data provide novel evidence that CRP exerts a proinflammatory action via TLR4-dependent signaling pathway (ATsub1/subR-p38 MAPK-TLR4-PKCα) in VSMCs.
机译:C反应蛋白(CRP)被认为在动脉粥样硬化期间诱导炎症反应。 Toll样受体4(TLR4)介导的炎症信号已显示促进动脉粥样硬化。 TLR4是否介导CRP的促炎作用仍是完全未知的。因此,本研究旨在探讨CRP在大鼠血管平滑肌细胞(VSMC)中与TLR4相关的促炎作用机制。 CRP可增加VSMC中血管内皮生长因子A(VEGF-A)和诱导型一氧化氮合酶(iNOS)的mRNA水平和蛋白质表达,并增强培养基中的NO分泌。但是,CRP阻碍了糖皮质激素受体(GR)的核转运,并降低了VSMC中GR的mRNA水平和蛋白质磷酸化。 TLR4小干扰RNA(siRNA)大大逆转了CRP的作用。这些表明,CRP能够通过VSMC中的TLR4诱导炎症反应。更重要的是,我们的数据提供了新的证据,表明CRP在VSMC中通过TLR4依赖性信号通路(AT 1 R-p38MAPK-TLR4-PKCα)发挥促炎作用。

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