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Mediators of Inflammation
Volume 7, Issue 2, Pages 85-91
http://dx.doi.org/10.1080/09629359891225

The role of cyclooxygenase-1 and cyclooxygenase-2 in lipopolysaccharide and interleukin-1 stimulated enterocyte prostanoid formation

Department of Surgery, Theodore Cooper Surgical Research Institute, St Louis University School of Medicine and Health Sciences Center, St Louis, mo 63110–0250, USA

Copyright © 1998 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Lipopolysaccharide is an inflammatory agent and interleukin-1 is a cytokine. Their pro-inflammatory effects may be mediated by prostanoids produced by inducible cyclooxygenase-2. The aim of this study was to determine the prostanoids produced by lipopolysaccharide and interleukin-1 stimulated enterocytes through the cyclooxygenase-1 and 2 pathways. Cultured enterocytes were stimulated with lipopolysaccharide or interleukin-1 β with and without cyclooxygenase inhibitors. Low concentrations of indomethacin and valerylsalicylic acid (VSA) were evaluated as cyclooxygenase-1 inhibitors and their effects compared with the effects of a specific cyclooxygenase-2 inhibitor, SC-58125. Prostaglandin E2 , 6-keto prostaglandin F , prostaglandin D2 and leukotriene B4 levels were determined by radio immunoassay. Immunoblot analysis using isoformspecific antibodies showed that the inducible cyclooxygenase enzyme (COX-2) was expressed by 4 h in LPS and IL-1β treated cells while the constitutive COX-1 remained unaltered in its expression. Interleukin-1β and lipopolysaccharide stimulated the formation of all prostanoids compared with untreated cells, but failed to stimulate leukotriene B4. Indomethacin at 20 μ M concentration, and VSA inhibited lipopolysaccharide and interleukin 1β stimulated prostaglandin E2 , but not 6-keto prostaglandin F formation. SC-58125 inhibited lipopolysaccharide and interleukin-1β stimulated 6-keto prostaglandin F but not prostaglandin E2 release. The specific cyclooxygenase-2 inhibitor also inhibited lipopolysaccharide produced prostaglandin D2 but not interleukin-1β stimulated prostaglandin D2 While SC-58125 inhibited basal 6-keto prostaglandin-F formation it significantly increased basal prostaglandin E2 and prostaglandin D2 formation. As SC-58125 inhibited lipopolysaccharide and interleukin-1β induced 6-keto prostaglandin F production but not prostaglandin E2 production, it suggests that these agents stimulate prostacyclin production through a cyclooxygenase-2 mediated mechanism and prostaglandin E2 production occurs through a cyclooxygenase-1 mediated mechanism. Prostaglandin D2 production appeared to be variably produced by cyclooxygenase-1 or cyclooxygenase-2, depending on the stimulus.