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KMID : 0043320080310101331
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Archives of Pharmacal Research
2008 Volume.31 No. 10 p.1331 ~ p.1338
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Regulation of Lysophosphatidic Acid-Induced COX-2 Expression by ERK1/2 Activation in Cultured Feline Esophageal Epithelial Cells
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Sohn Uy-Dong
Jeong Ji-Hoon
Song Hyun-Ju
Seo Jeong-Sook
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Abstract
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Lysophosphatidic acid (LPA), a potent bioactive phospholipid, mediates diverse cellular responses by binding to specific G protein-coupled receptors (GPCRs). We investigated the signaling mechanisms underlying LPA-induced COX-2 expression in primary cultures of feline esophageal epithelial cells. The identity of the cultures was confirmed by immunocytochemistry using a cytokeratin antibody. Western blot analysis revealed a concentration- and time- dependent induction of COX-2 in response to LPA. Of the three major MAPKs, only ERK1/2 was activated by LPA in a time-dependent manner. LPA-induced COX-2 expression was significantly attenuated by the MEK inhibitor, PD98059, but not by the JNK inhibitor, SP600125, or the p38 MAPK inhibitor, SB212090. LPA-induced COX-2 expression was repressed by pertussis toxin, GF109204X, and Ki16425, indicating the involvements of PTX-sensitive Gi/o protein, PKC, and the LPA1/3 receptor, respectively. Our data suggest that in esophageal epithelial cells, LPA-induced COX-2 expression requires activation of PKC and ERK1/2 downstream of the LPA1/3 receptor, Understanding the regulation of COX-2 expression induced by LPA in esophageal epithelial cells might provide a new therapeutic strategy for esophageal inflammatory diseases.
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KEYWORD
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LPA, COX-2 expression, Esophageal epithelial cells, ERK1/2
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