title: Toll-like receptor 4 mediates inflammatory cytokine secretion in smooth muscle cells induced by oxidized low-density lipoprotein.
abstract: Oxidized low-density lipoprotein (oxLDL)-regulated secretion of inflammatory cytokines in smooth muscle cells (SMCs) is regarded as an important step in the progression of atherosclerosis; however, its underlying mechanism remains unclear. This study investigated the role of toll-like receptor 4 (TLR4) in oxLDL-induced expression of inflammatory cytokines in SMCs both in vivo and in vitro. We found that the levels of TLR4, interleukin 1-β (IL1-β), tumor necrosis factor-α (TNFα), monocyte chemoattractant protein 1 (MCP-1) and matrix metalloproteinase-2 (MMP-2) expression were increased in the SMCs of atherosclerotic plaques in patients with femoral artery stenosis. In cultured primary arterial SMCs from wild type mice, oxLDL caused dose- and time-dependent increase in the expression levels of TLR4 and cytokines. These effects were significantly weakened in arterial SMCs derived from TLR4 knockout mice (TLR4-/-). Moreover, the secretion of inflammatory cytokines was blocked by TLR4-specific antibodies in primary SMCs. Ox-LDL induced activation of p38 and NFκB was also inhibited in TLR4-/- primary SMCs or when treated with TLR4-specific antibodies. These results demonstrated that TLR4 is a crucial mediator in oxLDL-induced inflammatory cytokine expression and secretion, and p38 and NFκB activation.
authors.affiliation: Institute of Cardiovascular Diseases, Medical School of Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Medical School of Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Xiao Jie
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Medical School of Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Li Juan
authors.initials: LJ
authors.lastname: Cao
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Medical School of Jiaotong University, Shanghai, People's Republic of China; Institute of Cardiovascular Diseases, Medical School of Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Xin He
authors.initials: XH
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Diseases, Medical School of Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Zhu Hui
authors.initials: ZH
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Diseases, Medical School of Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Xiao Qun
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Medical School of Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Qiu Jin
authors.initials: QJ
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Medical School of Jiaotong University, Shanghai, People's Republic of China; Institute of Cardiovascular Diseases, Medical School of Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Medical School of Jiaotong University, Shanghai, People's Republic of China; Institute of Cardiovascular Diseases, Medical School of Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Wei Feng
authors.initials: WF
authors.lastname: Shen
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Medical School of Jiaotong University, Shanghai, People's Republic of China; Institute of Cardiovascular Diseases, Medical School of Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D008077:Lipoproteins, LDL / Q000502:physiology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C099252:oxidized low density lipoprotein; D048051:p38 Mitogen-Activated Protein Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
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