Cyclooxygenase-2-derived prostaglandin D2is an early anti-inflammatory signal in experimental colitis

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.