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C-Reactive Protein Induces TNF-α Secretion by p38 MAPK–TLR4 Signal Pathway in Rat Vascular Smooth Muscle Cells

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Abstract

Atherosclerosis is a chronic inflammatory disease. C-reactive protein (CRP) not only is an inflammatory marker but also regulates the expressions of other inflammatory cytokines associated with the pathogenesis of atherosclerosis. Toll-like receptor 4 (TLR4) also contributes to atherogenesis via transducting inflammatory signals. Herein, our studies focused on characterizing the effect of CRP on tumor necrosis factor α (TNF-α) production and TLR4-related molecular mechanisms in rat vascular smooth muscle cells (VSMCs). The results showed that CRP stimulated VSMCs to secrete TNF-α and enhanced TLR4 expression in a time-concentration-dependent manner. TLR4 knockdown significantly inhibited CRP-induced TNF-α generation, and p38 mitogen-activated protein kinase (MAPK) blocker SB203580 depressed TLR4 expression and TNF-α production initiated by CRP in VSMCs. The data demonstrate that CRP triggers an inflammatory response in rat VSMCs by inducing TNF-α secretion, which is mediated by p38 MAPK–TLR4 signaling pathway.

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Acknowledgments

This study was supported by a grant from the National Natural Science Foundation of China to Juntian Liu (no. 30772567).

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Authors and Affiliations

  1. Department of Pharmacology, **’an Jiaotong University School of Medicine, **’an, 710061, People’s Republic of China

    Na Liu, Juntian Liu, Peipei Lu, Chen**g Wang & Fang Guo

  2. Scientific Research Center, The Second Affiliated Hospital, **’an Jiaotong University School of Medicine, **’an, 710004, People’s Republic of China

    Yuanyuan Ji

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  1. Na Liu
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Correspondence to Juntian Liu.

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Liu, N., Liu, J., Ji, Y. et al. C-Reactive Protein Induces TNF-α Secretion by p38 MAPK–TLR4 Signal Pathway in Rat Vascular Smooth Muscle Cells. Inflammation 34, 283–290 (2011). https://doi.org/10.1007/s10753-010-9234-z

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