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KMID : 0578320060220010044
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Molecules and Cells
2006 Volume.22 No. 1 p.44 ~ p.50
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Activation of p38 MAPK Is Involved in Endothelin-1-stimulated COX-2 Expression in Cultured Feline Esophageal Smooth Muscle Cells
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Song Hyun-Ju
Min Young-Sil
Shin Chang-Yell
Sohn Uy-Dong
Jeong Ji-Hoon
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Abstract
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We investigated the possible role of p38 MAPK and ETB receptors in ET-1 induction of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in cultured feline esophageal smooth muscle cells (ESMC). Confluent layers of ESMC were stimulated with 10 nM ET-1 and expression of COX-1 and COX-2, involvement of receptors, and activation of p38 MAPK, were examined by Western blot analysis. Levels of PGE2 induced by ET-1 were measured by Elisa. Using ETA and ETB antagonists (BQ-123 and BQ-788, respectively), the contribution of the ET receptors to COX-1 and COX-2 expression induced by ET-1 was determined. Western blot analysis revealed that treatment of ESMC with ET-1 resulted in transient expression of COX-2 and activation of p38 MAPK. Activation of p38 MAPK was maximal after 1 h. SB202190, a p38 MAPK inhibitor, reduced expression of COX-2, but not COX-1. ET-1-induced release of PGE2 was also blocked by SB202190. COX-2 expression was upregulated only via the ETB receptor, and COX-1 expression was not affected by either antagonist. Taken together, our data suggest that ET-1 causes p38 MAPK-dependent expression of COX-2 by interacting with ETB receptors on ESMC.
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KEYWORD
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Esophageal Smooth Muscle Cells, ET-1, ETB Receptor, p38 MAPK, PGE2
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