Toll-like receptor 4 mediates inflammatory cytokine secretion in smooth muscle cells induced by oxidized low-density lipoprotein

• Published in: PloS one Vol. 9; no. 4; p. e95935
• Main Authors: Yang, Ke, Zhang, Xiao Jie, Cao, Li Juan, Liu, Xin He, Liu, Zhu Hui, Wang, Xiao Qun, Chen, Qiu Jin, Lu, Lin, Shen, Wei Feng, Liu, Yan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2014; Public Library of Science (PLoS)
• Subjects: Activation; Aged; Analysis; Animals; Antibodies; Arteriosclerosis; Atherosclerosis; Biochemistry; Biology and Life Sciences; Cardiology; Cardiovascular disease; Care and treatment; Cells, Cultured; Cytokines; Cytokines - metabolism; Cytokines - secretion; Development and progression; Diagnosis; Femoral artery; Femur; Gelatinase A; Hospitals; Humans; Immune system; Immunoglobulins; Inflammation; Inflammation Mediators - physiology; Interleukin 1; Kinases; Lipoproteins; Lipoproteins, LDL - physiology; Low density lipoprotein; Low density lipoproteins; Male; Matrix metalloproteinase; Matrix Metalloproteinase 2 - metabolism; Medical schools; Medicine and Health Sciences; Metalloproteinase; Mice; Mice, Inbred C57BL; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Muscle, Smooth, Vascular - immunology; Muscle, Smooth, Vascular - pathology; Muscle, Smooth, Vascular - secretion; Muscles; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - secretion; NF-κB protein; Oxidation; p38 Mitogen-Activated Protein Kinases - metabolism; Penicillin; Physiological aspects; Physiology; Plaque, Atherosclerotic - immunology; Plaque, Atherosclerotic - metabolism; Plaque, Atherosclerotic - pathology; Plaques; Primary Cell Culture; Proteins; R&D; Research & development; Smooth muscle; Stenosis; TLR4 protein; Toll-Like Receptor 4 - physiology; Toll-like receptors; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumor necrosis factor-α; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0095935

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.