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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, C-Reactive Protein, Cells, Cultured, Gene Expression Regulation, Humans, I-kappa B Proteins, Inflammation, Interferon Regulatory Factor-3, Interleukin-6, Lipopolysaccharides, Male, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, NF-KappaB Inhibitor alpha, NF-kappa B, PPAR gamma, Phosphorylation, Polymyxin B, Proline, RNA, Small Interfering, Rats, Rats, Sprague-Dawley, Signal Transduction, Thiocarbamates, Toll-Like Receptor 4.
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Does c-reactive protein trigger inflammatory responses partly via TLR4/IRF3/NF-κB signaling pathway in rat vascular smooth muscle cells? Context: 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 γ (PPARγ), and TLR4-dependent signal pathway. rat VSMCs were cultured, and CRP was used as a stimulant for IL-6 and peroxisome proliferator-activated receptor γ (PPARγ). 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. CRP stimulated IL-6 secretion, and inhibited mRNA and protein expression of PPARγ in VSMCs in a concentration-dependent manner. Additionally, CRP induced TLR4 expression, promoted nuclear translocation of NF-κB (p65), and augmented IκBα phosphorylation in VSMCs. Taken together, CRP induces the inflammatory responses through increasing IL-6 generation and reducing PPARγ expression in VSMCs, which is mediated by TLR4/IRF3/NF-κB signal pathway.
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CRP is able to stimulate IL-6 production and to inhibit PPARγ expression in VSMCs via MyD88-independent TLR4 signaling pathway (TLR4/IRF3/NF-κB). These provide the novel evidence for the pro-inflammatory action of CRP involved in atherogenesis. Final Decision: yes