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Abstract The intestinal cell line I407 responds to basic fibroblast growth factor (bFGF) by upregulating cyclooxygenase-2 (COX-2) mRNA and protein expression and increasing PGE 2 production. bFGF treatment of I407 cells results in phosphorylation of p38, and the p38 inhibitor SB-203580 abrogates bFGF-induced PGE 2 synthesis. Wild-type p38α (p38αWT) and dominant-negative p38α (p38αDN) stable transfectant clones of I407 cells were used to examine the role of the p38 MAP kinase pathway in the events controlling PGE 2 synthesis after treatment with bFGF. Treatment of p38αWT clones with bFGF resulted in increased COX-2 protein levels and PGE 2 synthesis similar to those seen in bFGF-treated control-transfected cells. In contrast, the p38αDN clones failed to upregulate COX-2 protein or increase PGE 2 synthesis when treated with bFGF. Exogenous arachidonate did not restore PGE 2 synthesis by p38αDN cells. bFGF treatment increased COX-2 mRNA stability, and the p38 inhibitor SB-203580 attenuated COX-2 mRNA stability in bFGF-treated I407 cells. These data demonstrate a crucial role for p38α in growth factor-induced PGE 2 synthesis by intestinal cells. Furthermore, they indicate that p38 activity is required at a step distal to arachidonate release, most likely COX-2 upregulation, because exogenous arachidonate did not restore PGE 2 synthesis. intestinal epithelial cells intestinal injury and repair arachidonic acid metabolism mRNA stability. Footnotes This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants R01-DK-33165 and R01-DK-55753 (to W. F. Stenson), RO1-DK-50924 (to S. M. Cohn), and DK-52574 (to the Washington Univ. Digestive Disease Center). Address for reprint requests and other correspondence: T. G. Tessner, Gastroenterology, Campus Box 8124, Washington Univ. School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110 (E-mail: stensnlb@im.wustl.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. First published October 9, 2002;10.1152/ajpgi.00226.2002 Copyright © 2003 the American Physiological Society
AJP - Gastrointestinal and Liver Physiology – The American Physiological Society
Published: Feb 1, 2003
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