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.
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.
Moon
Yuseok
Y
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
Lee
Myoungjoo
M
Yang
Hyun
H
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
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