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The inhibition of TNFα‐induced monocyte chemoattractant protein‐1 production by epigallocatechin‐3‐O‐gallate in vascular endothelial cells
Author(s) -
Ahn Hee Yul,
Xu Yi,
Davidge Sandra T
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a700
Subject(s) - wortmannin , chemistry , monocyte , tumor necrosis factor alpha , protein kinase b , epigallocatechin gallate , p38 mitogen activated protein kinases , protein kinase a , ly294002 , pi3k/akt/mtor pathway , kinase , gallate , signal transduction , cancer research , pharmacology , microbiology and biotechnology , medicine , endocrinology , biochemistry , biology , antioxidant , polyphenol
Monocyte chemoattractant protein‐1 (MCP‐1) plays a pivotal role in the recruitment of monocytes and in the development of atherosclerosis. Epigallocatechin‐3‐O‐gallate (EGCG), the major catechin derived from green tea, has multiple pharmacologic effects. In this study, we investigated the mechanism(s) by which EGCG inhibits TNFα‐induced MCP‐1 production in bovine coronary artery endothelial cell (BCAEC). TNFα (5 ng/ml) increased MCP‐1 production (284±19%, n=6, P<0.001) in BCAEC. EGCG (40 μM) significantly attenuated TNFα‐induced MCP‐1 production (31±11%, n=9, P<0.001). On the other hand, inhibitors of MEK (PD98059, 50 μM), PI‐3 kinase (LY294002, 10 μM; wortmannin, 20 nM), c‐Jun N‐terminal kinase (SP600125, 20 μM), but not p38 MAPK (SB203580, 10 μM), decreased TNFα‐induced MCP‐1 production . Interestingly, EGCG markedly reduced phosphoryaltion of Akt by TNFα. Conclusions EGCG decreased TNFα‐induced MCP‐1 production in BCAEC . The mechanism for TNFα effect of MCP‐1 in endothelial cell involves Erk1/2, PI‐3 kinase and c‐Jun N‐terminal kinase pathways. Determining the effect of EGCG on these signaling pathway will contribute to understanding its beneficial effects on cardiovascular disease. Dr. HYA is a recipient of visiting scholarship from Alberta Heritage Foundation for Medical Research