Cyclooxygenase-2-derived prostaglandin D2is an early anti-inflammatory signal in experimental colitis
- 1 July 2000
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Gastrointestinal and Liver Physiology
- Vol. 279 (1) , G238-G244
- https://doi.org/10.1152/ajpgi.2000.279.1.g238
Abstract
The ability of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors to exacerbate inflammatory bowel disease suggests that prostaglandins are important anti-inflammatory mediators in this context. Prostaglandin D2has been suggested to exert anti-inflammatory effects. We investigated the possibility that prostaglandin D2derived from cyclooxygenase-2 plays an important role in downregulating colonic inflammation in rats. Colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid. At various times thereafter (from 1 h to 7 days), colonic prostaglandin synthesis and myeloperoxidase activity (index of granulocyte infiltration) were measured. Prostaglandin D2synthesis was elevated >4-fold above controls within 1–3 h of induction of colitis, preceding significant granulocyte infiltration. Treatment with a selective cyclooxygenase-2 inhibitor abolished the increase in prostaglandin D2synthesis and caused a doubling of granulocyte infiltration. Colonic granulocyte infiltration was significantly reduced by administration of prostaglandin D2or a DP receptor agonist (BW-245C). These results demonstrate that induction of colitis results in a rapid increase in prostaglandin D2synthesis via cyclooxygenase-2. Prostaglandin D2downregulates granulocyte infiltration into the colonic mucosa, probably through the DP receptor.Keywords
This publication has 33 references indexed in Scilit:
- Selective cyclo‐oxygenase‐2 inhibition with celecoxib elevates blood pressure and promotes leukocyte adherenceBritish Journal of Pharmacology, 2000
- Cyclo‐oxygenase‐2: pharmacology, physiology, biochemistry and relevance to NSAID therapyBritish Journal of Pharmacology, 1999
- Selective COX‐2 inhibitors and human inflammatory bowel diseaseAlimentary Pharmacology & Therapeutics, 1999
- PPARγ-Ligands Inhibit Migration Mediated by Multiple Chemoattractants in Vascular Smooth Muscle CellsJournal of Cardiovascular Pharmacology, 1999
- Limited anti‐inflammatory efficacy of cyclo‐oxygenase‐2 inhibition in carrageenan‐airpouch inflammationBritish Journal of Pharmacology, 1999
- Contribution of cyclooxygenase-1 and cyclooxygenase-2 to prostanoid formation by human enterocytes stimulated by calcium ionophore and inflammatory agentsProstaglandins & Other Lipid Mediators, 1998
- Peroxisome Proliferator-activated Receptors α and γ Are Activated by Indomethacin and Other Non-steroidal Anti-inflammatory DrugsJournal of Biological Chemistry, 1997
- Prostaglandin protection of rat colonic mucosa from damage induced by ethanolDigestive Diseases and Sciences, 1985
- Analgesic ingestion and other factors preceding relapse in ulcerative colitis.Gut, 1983
- INCREASED PROSTAGLANDIN PRODUCTION IN ULCERATIVE COLITISThe Lancet, 1977