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Contribution of cyclooxygenase-1 and cyclooxygenase-2 to prostanoid formation by human enterocytes stimulated by calcium ionophore and inflammatory agents.
Prostaglandins Other Lipid Mediat. 1998 Aug; 56(5-6):325-39.PO

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)beta (IL-1 beta), 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-1 beta, and Ca Ion, but not LPS, increased prostaglandin F2 alpha (PGF2 alpha) formation. Ca Ion-stimulated prostanoid formation was uniformly inhibited by COX-2, but not COX-1, inhibitors. IL-1 beta-stimulated PGE2 and PGE2 alpha formation was significantly decreased by both COX-1 and COX-2 inhibitors. VSA, in a dose-dependent manner, significantly decreased IL-1 beta-stimulated PGE2 and PGF2 alpha 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 PGF2 alpha 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.

Authors+Show Affiliations

Department of Surgery, Theodore Cooper Surgical Research Institute, Saint Louis University School of Medicine and Health Sciences Center, Missouri, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9990676

Citation

Longo, W E., et al. "Contribution of Cyclooxygenase-1 and Cyclooxygenase-2 to Prostanoid Formation By Human Enterocytes Stimulated By Calcium Ionophore and Inflammatory Agents." Prostaglandins & Other Lipid Mediators, vol. 56, no. 5-6, 1998, pp. 325-39.
Longo WE, Panesar N, Mazuski J, et al. Contribution of cyclooxygenase-1 and cyclooxygenase-2 to prostanoid formation by human enterocytes stimulated by calcium ionophore and inflammatory agents. Prostaglandins Other Lipid Mediat. 1998;56(5-6):325-39.
Longo, W. E., Panesar, N., Mazuski, J., & Kaminski, D. L. (1998). Contribution of cyclooxygenase-1 and cyclooxygenase-2 to prostanoid formation by human enterocytes stimulated by calcium ionophore and inflammatory agents. Prostaglandins & Other Lipid Mediators, 56(5-6), 325-39.
Longo WE, et al. Contribution of Cyclooxygenase-1 and Cyclooxygenase-2 to Prostanoid Formation By Human Enterocytes Stimulated By Calcium Ionophore and Inflammatory Agents. Prostaglandins Other Lipid Mediat. 1998;56(5-6):325-39. PubMed PMID: 9990676.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Contribution of cyclooxygenase-1 and cyclooxygenase-2 to prostanoid formation by human enterocytes stimulated by calcium ionophore and inflammatory agents. AU - Longo,W E, AU - Panesar,N, AU - Mazuski,J, AU - Kaminski,D L, PY - 1999/2/17/pubmed PY - 1999/2/17/medline PY - 1999/2/17/entrez SP - 325 EP - 39 JF - Prostaglandins & other lipid mediators JO - Prostaglandins Other Lipid Mediat. VL - 56 IS - 5-6 N2 - 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)beta (IL-1 beta), 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-1 beta, and Ca Ion, but not LPS, increased prostaglandin F2 alpha (PGF2 alpha) formation. Ca Ion-stimulated prostanoid formation was uniformly inhibited by COX-2, but not COX-1, inhibitors. IL-1 beta-stimulated PGE2 and PGE2 alpha formation was significantly decreased by both COX-1 and COX-2 inhibitors. VSA, in a dose-dependent manner, significantly decreased IL-1 beta-stimulated PGE2 and PGF2 alpha 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 PGF2 alpha 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. SN - 1098-8823 UR - https://www.unboundmedicine.com/medline/citation/9990676/Contribution_of_cyclooxygenase_1_and_cyclooxygenase_2_to_prostanoid_formation_by_human_enterocytes_stimulated_by_calcium_ionophore_and_inflammatory_agents_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0090-6980(98)00058-6 DB - PRIME DP - Unbound Medicine ER -