Regulation of lysophosphatidic acid-induced COX-2 expression by ERK1/2 activation in cultured feline esophageal epithelial Cells |
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Authors: | Do Young Kim Hyun Ju Song Ji Hoon Jeong Jung Sook Suh Uy Dong Sohn |
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Institution: | (1) Department of Pharmacology, College of Medicine, Chung Ang University, Seoul, 156-756, Korea;(2) Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul, 156-756, Korea |
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Abstract: | 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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Keywords: | LPA COX-2 expression Esophageal epithelial cells ERK1/2 |
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