Toll-like receptor 4 signaling mediates inflammatory activation induced by C-reactive protein in vascular smooth muscle cells.

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.