Liu Na, Liu Juntian, Ji Yuanyuan, Lu Peipei
Department of Pharmacology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, China.
Cell Physiol Biochem. 2010;25(4-5):467-76. doi: 10.1159/000303052. Epub 2010 Mar 23.
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 (AT(1)R-p38 MAPK-TLR4-PKCalpha) in VSMCs.
C反应蛋白（CRP）被认为在动脉粥样硬化过程中诱导炎症反应。Toll样受体4（TLR4）介导的炎症信号已被证明促进动脉粥样硬化的发生。TLR4是否介导CRP的促炎作用仍完全未知。因此，本研究旨在探讨CRP在大鼠血管平滑肌细胞（VSMCs）中促炎作用的TLR4相关机制。CRP增加了VSMCs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水平和蛋白表达，并增强了培养基中的NO分泌。但是，CRP阻碍了糖皮质激素受体（GR）的核转位，并降低了VSMCs中GR的mRNA水平和蛋白磷酸化。TLR4小干扰RNA（siRNA）显著逆转了CRP的作用。这些表明CRP能够通过VSMCs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，即CRP通过VSMCs中TLR4依赖性信号通路（AT(1)R-p38 MAPK-TLR4-PKCalpha）发挥促炎作用。
