Green Tea Research Today is a free monthly online journal that collates and summarizes the latest research about Green Tea, including details on benefits, antioxidants, weight loss, diet, side effects. | ||||||||
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Involvement of early growth response gene 1 in the modulation of microsomal prostaglandin E synthase 1 by epigallocatechin gallate in A549 human pulmonary epithelial cells.Moon Y, Lee M, Yang H Department of Microbiology and Immunology and Medical Research Institute, Pusan National University School of Medicine, Busan 602-739, Republic of Korea. moon@pusan.ac.kr The prostaglandin E(2) (PGE(2)) can play critical roles in the pulmonary inflammation or carcinogenesis. It is the first investigation of the effect of a green tea polyphenol, (-)-epigallocatechin gallate (EGCG), on the PGE(2)-producing microsomal prostaglandin E synthase 1 (mPGES-1) expression in the lung alveolar type II pneumocytes, A549 cells as an epithelial model. EGCG enhanced cyclooxygenase (COX)-2 and mPGES-1 gene expression as well as PGE(2). Among several tea catechins, EGCG was most effective in inducing mPGES-1 expression. Moreover, even in the cytokine-stimulated cells, mPGES-1 protein was super-induced by EGCG treatment. As signaling mediators in mPGES-1 induction by EGCG, active ERK1/2 MAP kinases and early growth response gene 1 (EGR-1) were increased after exposure to EGCG. Moreover, EGCG stimulated the nuclear translocation of the EGR-1 protein in A549 cells through ERK signaling pathway. Recent studies demonstrate that EGR-1 is a key transcription factor in mPGES-1 gene expression. When blocking the gene expression of EGR-1 with EGR-1 siRNA or ERK inhibitor, EGCG-induced mPGES-1 was suppressed in both cases. mPGES-1 promoter with deleted or point-mutated EGR-1 binding sites showed significantly less response to the EGCG stimulation, which also implicated the importance of EGR-1 binding in promoting mPGES-1 gene expression. Taken all, EGCG was strong inducer of EGR-1 expression and mediated EGR-1 nuclear translocation via ERK signaling pathway in A549 pulmonary epithelial cells. Induced EGR-1 then stimulated the induction of mPGES-1 gene expression and this effect mechanistically can be linked to the pharmacological or toxicological actions after human exposure to green tea catechins. Published 12 December 2006 in Biochem Pharmacol, 73(1): 125-35.
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