title: Epigallocatechin-3-O-gallate inhibits TNFalpha-induced monocyte chemotactic protein-1 production from vascular endothelial cells.
abstract: Monocyte chemotactic protein-1 (MCP-1) plays a pivotal role in the recruitment of monocytes and thus in the development of inflammatory cardiovascular diseases. Epigallocatechin-3-O-gallate (EGCG), the major catechin derived from green tea, has multiple beneficial effects to reduce cardiovascular disease but the effects of EGCG on vascular endothelial MCP-1 production is not known. In this study, we investigated the mechanisms by which EGCG may inhibit tumor necrosis factor-alpha (TNFalpha)-induced MCP-1 production in bovine coronary artery endothelial cells. TNFalpha increased MCP-1 production in both a concentration and time-dependent manner. Inhibitors of phosphatidylinositol-3-OH kinase (PI-3 kinase), LY294002 and wortmannin, decreased TNFalpha-induced MCP-1 production. EGCG prevented TNFalpha-mediated MCP-1 production and reduced phosphorylation of Akt (Ser473). In addition, EGCG attenuated TNFalpha mediated down-regulation of TNFalpha receptor 1 (TNFR1), but not TNFR2. In conclusion, EGCG inhibited TNFalpha-induced MCP-1 production. Moreover, EGCG inhibited Akt phosphorylation as well as TNF activation of TNFR1, which subsequently resulted in reduced MCP-1 production. These data provide a novel mechanism where the green tea flavonoid, EGCG, could provide direct vascular benefits in inflammatory cardiovascular diseases.
authors.affiliation: Department of Obstetrics and Gynecology, Perinatal Research Centre, University of Alberta, Edmonton, Canada, T6G 2S2.
authors.forename: Hee Yul
authors.initials: HY
authors.lastname: Ahn
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Davidge
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D002867:Chromones / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D013662:Tea / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: D018932:Chemokine CCL2; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013662:Tea; D014409:Tumor Necrosis Factor-alpha; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D002392:Catechin; C045651:epigallocatechin gallate; D051058:Oncogene Protein v-akt