Basic fibroblast growth factor upregulates cyclooxygenase-2 in I407 cells through p38 MAP kinase

Teresa G. Tessner, Filipe Muhale, Suzanne Schloemann, Steven Cohn, Aubrey Morrison, William F. Stenson

Research output: Contribution to journalArticle

23 Scopus citations

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 PGE2 production. bFGF treatment of I407 cells results in phosphorylation of p38, and the p38 inhibitor SB-203580 abrogates bFGF-induced PGE2 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 PGE2 synthesis after treatment with bFGF. Treatment of p38αWT clones with bFGF resulted in increased COX-2 protein levels and PGE2 synthesis similar to those seen in bFGF-treated control-transfected cells. In contrast, the p38αDN clones failed to upregulate COX-2 protein or increase PGE2 synthesis when treated with bFGF. Exogenous arachidonate did not restore PGE2 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 p38a in growth factor-induced PGE2 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 PGE2 synthesis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume284
Issue number2 47-2
StatePublished - Feb 1 2003
Externally publishedYes

Keywords

  • Arachidonic acid metabolism
  • Intestinal epithelial cells
  • Intestinal injury and repair
  • mRNA stability

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

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