title: LPS induces inflammatory responses in human aortic vascular smooth muscle cells via Toll-like receptor 4 expression and nitric oxide production.
abstract: Inflammation is an important event in the development of vascular diseases such as hypertension, atherosclerosis, and restenosis. In addition, the stimulation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) induces the release of critical proinflammatory cytokines that activate potent immune responses. In this study, LPS was found to induce TLR4 expression and increased nitric oxide (NO) production by increasing the expression of inducible nitric oxide synthase (iNOS). Furthermore, LPS was found to induce interleukin (IL)-8 and vascular endothelial growth factor (VEGF) production, as well as intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression. Taken together, these results indicate that LPS induces inflammatory responses in HASMC. Moreover, NOS inhibitor (L-NAME) and anti-TLR 4mAb reduced the LPS-induced NO, IL-8 and VEGF production and ICAM-1 expression. Additionally, TLR4 expression was reduced by NOS inhibitor. Taken together, these results indicate that LPS-induced inflammatory responses are regulated by TLR4 expression and NO production.
authors.affiliation: Cardiovascular Medical Research Center and Department of Prescriptionology, University of Dongguk, Gyeongju City, Gyeongbuk 780-714, Republic of Korea.
authors.forename: Sook-Kyoung
authors.initials: SK
authors.lastname: Heo
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Yun
authors.forename: Eui-Kyu
authors.initials: EK
authors.lastname: Noh
authors.forename: Won-Hwan
authors.initials: WH
authors.lastname: Park
authors.forename: Sun-Dong
authors.initials: SD
authors.lastname: Park
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000187:drug effects*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; C508606:CXCL8 protein, human; D004791:Enzyme Inhibitors; D016209:Interleukin-8; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; C467484:VEGFA protein, human; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester