title: Reduction of monocyte chemoattractant protein-1 and interleukin-8 levels by ticlopidine in TNF-alpha stimulated human umbilical vein endothelial cells.
abstract: Atherosclerosis and its associated complications represent major causes of morbidity and mortality in the industrialized or Western countries. Monocyte chemoattractant protein-1 (MCP-1) is critical for the initiating and developing of atherosclerotic lesions. Interleukin-8 (IL-8), a CXC chemokine, stimulates neutrophil chemotaxis. Ticlopidine is one of the antiplatelet drugs used to prevent thrombus formation relevant to the pathophysiology of atherothrombosis. In this study, we found that ticlopidine dose-dependently decreased the mRNA and protein levels of TNF-alpha-stimulated MCP-1, IL-8, and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Ticlopidine declined U937 cells adhesion and chemotaxis as compared to TNF-alpha stimulated alone. Furthermore, the inhibitory effects were neither due to decreased HUVEC viability, nor through NF-kB inhibition. These results suggest that ticlopidine decreased TNF-alpha induced MCP-1, IL-8, and VCAM-1 levels in HUVECs, and monocyte adhesion. Therefore, the data provide additional therapeutic machinery of ticlopidine in treatment and prevention of atherosclerosis.
authors.affiliation: Department of Neurology, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Chaur-Jong
authors.initials: CJ
authors.lastname: Hu
authors.forename: Yueh-Lun
authors.initials: YL
authors.lastname: Lee
authors.forename: Neng-Yao
authors.initials: NY
authors.lastname: Shih
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Yang
authors.forename: Suparat
authors.initials: S
authors.lastname: Charoenfuprasert
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Dai
authors.forename: Su-Mei
authors.initials: SM
authors.lastname: Chang
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Tsai
authors.forename: How
authors.initials: H
authors.lastname: Tseng
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Liu
authors.forename: Sy-Jye
authors.initials: SJ
authors.lastname: Leu
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013988:Ticlopidine / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D016209:Interleukin-8; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D013988:Ticlopidine