PMID- 18397796 OWN - NLM STAT- MEDLINE DCOM- 20080617 LR - 20191210 IS - 0024-3205 (Print) IS - 0024-3205 (Linking) VI - 82 IP - 17-18 DP - 2008 Apr 23 TI - Epigallocatechin-3-O-gallate inhibits TNFalpha-induced monocyte chemotactic protein-1 production from vascular endothelial cells. PG - 964-8 LID - 10.1016/j.lfs.2008.02.018 [doi] AB - 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. FAU - Ahn, Hee Yul AU - Ahn HY AD - Department of Obstetrics and Gynecology, Perinatal Research Centre, University of Alberta, Edmonton, Canada, T6G 2S2. FAU - Xu, Yi AU - Xu Y FAU - Davidge, Sandra T AU - Davidge ST LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080308 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Chemokine CCL2) RN - 0 (Chromones) RN - 0 (Enzyme Inhibitors) RN - 0 (Morpholines) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Tea) RN - 0 (Tumor Necrosis Factor-alpha) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - 8R1V1STN48 (Catechin) RN - BQM438CTEL (epigallocatechin gallate) RN - EC 2.7.11.1 (Oncogene Protein v-akt) SB - IM MH - Animals MH - Catechin/*analogs & derivatives/pharmacology MH - Cattle MH - Cell Line MH - Chemokine CCL2/*biosynthesis MH - Chromones/pharmacology MH - Endothelial Cells/drug effects/*metabolism MH - Endothelium, Vascular/cytology/drug effects/*metabolism MH - Enzyme Inhibitors/pharmacology MH - Morpholines/pharmacology MH - Oncogene Protein v-akt/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Phosphorylation/drug effects MH - Tea/chemistry MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/*pharmacology EDAT- 2008/04/10 09:00 MHDA- 2008/06/18 09:00 CRDT- 2008/04/10 09:00 PHST- 2007/10/30 00:00 [received] PHST- 2008/02/27 00:00 [revised] PHST- 2008/02/29 00:00 [accepted] PHST- 2008/04/10 09:00 [pubmed] PHST- 2008/06/18 09:00 [medline] PHST- 2008/04/10 09:00 [entrez] AID - S0024-3205(08)00110-0 [pii] AID - 10.1016/j.lfs.2008.02.018 [doi] PST - ppublish SO - Life Sci. 2008 Apr 23;82(17-18):964-8. doi: 10.1016/j.lfs.2008.02.018. Epub 2008 Mar 8.