Acid-induced COX-2 Expression and Prostaglandin E-2 Production via Activation of ERK1/2 and p38 MAPK in Cultured Feline Esophageal Smooth Muscle Cells

Abstract

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.