Regulation of lysophosphatidic acid-induced COX-2 expression by ERK1/2 activation in cultured feline esophageal epithelial cells.
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 G(i/o) protein, PKC, and the LPA(1/3) 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 LPA(1/3) 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.
Kim
Do Young
DY
Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 156-756, Korea.
Song
Hyun Ju
HJ
Jeong
Ji Hoon
JH
Suh
Jung Sook
JS
Sohn
Uy Dong
UD
D000818:Animals; D015153:Blotting, Western; D002415:Cats; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology*; D004947:Esophagus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D007150:Immunohistochemistry; D008246:Lysophospholipids / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000096:biosynthesis
D008246:Lysophospholipids; D051546:Cyclooxygenase 2; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C032881:lysophosphatidic acid