Acid-induced COX-2 expression and prostaglandin E2 production via activation of ERK1/2 and p38 MAPK in cultured feline esophageal smooth muscle cells.
Cyclooxygenase (COX)-2 is known to play an important role in inflammatory conditions such as reflux esophagitis resulting from acid reflux. In this study, we tested whether an acidic medium (pH 4.0) induces an increase in COX-2 expression or PGE(2) production, and explored the implication of mitogen-activated protein kinases (MAPKs) activation in these responses in cultured cat esophageal smooth muscle cells. Acidic cytotoxicity was assessed and expression changes in COXs or phosphorylated MAPKs were analyzed by Western blotting. PGE(2) production was measured by immunoassay. No significant decrease in cell viability was observed for 6 h exposure to acidic medium. COX-2 expression and PGE(2) production significantly increased to maximal levels at 6 h exposure to acidic medium. The cells also exhibited significant activation of ERK1/2 and p38 MAPK, but not JNK within 10 min under acidic medium. The increments of COX-2 expression and PGE(2) production by acidic medium were decreased by pretreatment with PD98059 or SB202190, respectively. These results suggest that acidic environments may enhance the COX-2 expression and PGE(2) production through activation of ERK1/2 and p38 MAPK in the cultured cat esophageal smooth muscle cells.
Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 156-756, Korea.
Jae Gwang
JG
Woo
Sun Young
SY
Park
Jae Chun
JC
Lim
Min-Jae
MJ
Joo
Hak Rim
HR
Kim
Uy Dong
UD
Sohn
D000143:Acids / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D002470:Cell Survival; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004789:Enzyme Activation; D004947:Esophagus / Q000166:cytology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006863:Hydrogen-Ion Concentration; D020935:MAP Kinase Signaling System; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000143:Acids; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone