Contribution of cyclooxygenase-1 and cyclooxygenase-2 to prostanoid formation by human enterocytes stimulated by calcium ionophore and inflammatory agents

Walter E. Longo, Ninder Panesar, John Mazuski, Donald L. Kaminski

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The stimulation of intestinal epithelial cell cyclooxygenase (COX) enzymes with inflammatory agents and the inhibition of COX-1 and COX-2 enzymes has the potential to increase understanding of the role of these enzymes in intestinal inflammation. The aim of this study was to determine the contributions of COX-1 and -2 to the production of specific prostanoids by unstimulated and stimulated intestinal epithelial cells. Cultured enterocytes were stimulated with lipopolysaccharide (LPS), interleukin-1 (IL- 1)β (IL-1β), and calcium ionophore (Ca Ion), with and without COX inhibitors. Valerylsalicylic acid (VSA) was employed as the COX-1 inhibitor, and SC-58125 and NS398 were used as the COX-2 inhibitors. Prostanoids were quantitated by Elisa assay. Western immunoblotting demonstrated the presence of constitutive COX-1 and inducible COX-2 enzyme. Unstimulated prostanoid formation was not decreased by the COX-1 inhibitor. All of the stimulants evaluated increased prostaglandin E2 (PGE2) production. Only Ca Ion stimulated prostaglandin D2 (PGD2) production while IL-1β, and Ca Ion, but not LPS, increased prostaglandin F(2α) (PGF(2α)) formation. Ca Ion- stimulated prostanoid formation was uniformly inhibited by COX-2, but not COX-1, inhibitors. IL-1β-stimulated PGE2 and PGF(2α) formation was significantly decreased by both COX-1 and COX-2 inhibitors. VSA, in a dose- dependent manner, significantly decreased IL-1β-stimulated PGE2 and PGF(2α) production. Unstimulated prostanoid formation was not dependent on constitutive COX-1 activity. The stimulation of intestinal epithelial cells by Ca Ion seemed to uniformly produce prostanoids through COX-2 activity. There was no uniform COX-1 or COX-2 pathway for PGE and PGF(2α) formation stimulated by the inflammatory agents, suggesting that employing either a COX-1 or COX-2 inhibitor therapeutically will have varying effects on intestinal epithelial cells dependent on the prostanoid species and the inflammatory stimulus involved.

Original languageEnglish
Pages (from-to)325-339
Number of pages15
JournalProstaglandins and Other Lipid Mediators
Volume56
Issue number5-6
DOIs
StatePublished - 1998

Keywords

  • Calcium ionophore
  • Cyclooxygenase-1
  • Cyclooxygenase-2
  • Enterocytes
  • Human
  • Inflammatory agents
  • Prostanoid formation

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