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C-reactive protein triggers inflammatory responses partly via TLR4/IRF3/NF-kappaB signaling pathway in rat vascular smooth muscle cells.

Authors: Liu, N  Liu, JT  Ji, YY  Lu, PP 
Citation: Liu N, etal., Life Sci. 2010 Sep 11;87(11-12):367-74. Epub 2010 Aug 4.
Pubmed: (View Article at PubMed) PMID:20670634
DOI: Full-text: DOI:10.1016/j.lfs.2010.07.012

AIMS: C-reactive protein (CRP) plays an important role in the inflammatory process of atherosclerosis. Toll-like receptor 4 (TLR4) participates in atherogenesis by mediating the inflammatory responses. The aim of this experiment was to investigate the pro-inflammatory effects and mechanisms of CRP in rat vascular smooth muscle cells (VSMCs), especially focusing on the effects of CRP on IL-6 and peroxisome proliferator-activated receptor gamma (PPARgamma), and TLR4-dependent signal pathway. MAIN METHODS: rat VSMCs were cultured, and CRP was used as a stimulant for IL-6 and peroxisome proliferator-activated receptor gamma (PPARgamma). IL-6 level in the culture supernatant was measured by ELISA, and mRNA and protein expressions were assayed by quantitative real-time PCR and western blot, respectively. RNA interference was used to assess the roles of TLR4 and interferon regulatory factor 3 (IRF3) in the pro-inflammatory signal pathway of CRP. KEY FINDINGS: CRP stimulated IL-6 secretion, and inhibited mRNA and protein expression of PPARgamma in VSMCs in a concentration-dependent manner. Additionally, CRP induced TLR4 expression, promoted nuclear translocation of NF-kappaB (p65), and augmented IkappaBalpha phosphorylation in VSMCs. Taken together, CRP induces the inflammatory responses through increasing IL-6 generation and reducing PPARgamma expression in VSMCs, which is mediated by TLR4/IRF3/NF-kappaB signal pathway. SIGNIFICANCE: CRP is able to stimulate IL-6 production and to inhibit PPARgamma expression in VSMCs via MyD88-independent TLR4 signaling pathway (TLR4/IRF3/NF-kappaB). These provide the novel evidence for the pro-inflammatory action of CRP involved in atherogenesis.


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CRRD Object Information
CRRD ID: 5128809
Created: 2011-03-17
Species: All species
Last Modified: 2011-03-17
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.