Cyclooxygenase-2-derived prostaglandin D 2 is an early anti-inflammatory signal in experimental colitis

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2000-07, Vol.279 (1), p.G238-G244
• Main Authors: Ajuebor, Maureen N., Singh, Anita, Wallace, John L.
• Format: Article
• Language: English
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.2000.279.1.G238

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 D 2 has been suggested to exert anti-inflammatory effects. We investigated the possibility that prostaglandin D 2 derived 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 D 2 synthesis 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 D 2 synthesis and caused a doubling of granulocyte infiltration. Colonic granulocyte infiltration was significantly reduced by administration of prostaglandin D 2 or a DP receptor agonist (BW-245C). These results demonstrate that induction of colitis results in a rapid increase in prostaglandin D 2 synthesis via cyclooxygenase-2. Prostaglandin D 2 downregulates granulocyte infiltration into the colonic mucosa, probably through the DP receptor.