title: 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.
abstract: 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.
authors.affiliation: 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
authors.forename: Yuseok
authors.initials: Y
authors.lastname: Moon
authors.forename: Myoungjoo
authors.initials: M
authors.lastname: Lee
authors.forename: Hyun
authors.initials: H
authors.lastname: Yang
mesh_terms: D001483:Base Sequence; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D017931:DNA Primers; D051766:Early Growth Response Protein 1 / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D018613:Microscopy, Confocal; D008861:Microsomes / Q000201:enzymology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D000071876:Prostaglandin-E Synthases; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D002392:Catechin; C045651:epigallocatechin gallate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases