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

The ability of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 in hibitors to exacerbate inflammatory bowel disease suggests that prostagland ins are important anti-inflammatory mediators in this context. Prostaglandi n D-2 has been suggested to exert anti-inflammatory effects. We investigate d the possibility that prostaglandin D-2 derived from cyclooxygenase-2 play s an important role in downregulating colonic inflammation in rats. Colitis was induced by intracolonic administration of trinitrobenzene sulfonic aci d. 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 contr ols within 1-3 h of induction of colitis, preceding significant granulocyte infiltration. Treatment with a selective cyclooxygenase-2 inhibitor abolis hed the increase in prostaglandin D-2 synthesis and caused a doubling of gr anulocyte 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 ra pid increase in prostaglandin D-2 synthesis via cyclooxygenase-2. Prostagla ndin D-2 downregulates granulocyte infiltration into the colonic mucosa, pr obably through the DP receptor.