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KMID : 0043320110340122131
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Archives of Pharmacal Research
2011 Volume.34 No. 12 p.2131 ~ p.2140
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Acid-induced COX-2 expression and prostaglandin E2 production via activation of ERK1/2 and p38 MAPK in cultured feline esophageal smooth muscle cells
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Woo Jae-Gwang
Park Sun-Young
Lim Jae-Chun
Joo Min-jae
Kim Hak-Rim
Sohn Uy-Dong
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Abstract
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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 PGE2 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. PGE2 production was measured by immunoassay. No significant decrease in cell viability was observed for 6 h exposure to acidic medium. COX-2 expression and PGE2 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 PGE2 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 PGE2 production through activation of ERK1/2 and p38 MAPK in the cultured cat esophageal smooth muscle cells.
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KEYWORD
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Smooth muscle cell, Acid, Cyclooxygenase-2, Prostaglandin E2, MAPK, Esophagitis
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