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 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.
Ajuebor
M N
MN
Mucosal Inflammation Research Group, University of Calgary, Alberta, Canada.
Singh
A
A
Wallace
J L
JL
D000818:Animals; D015153:Blotting, Western; D000068579:Celecoxib; D003092:Colitis / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D006827:Hydantoins / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D054834:Lipocalins; D008297:Male; D009336:Necrosis; D009504:Neutrophils / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D020675:Peroxisomes / Q000201:enzymology; D015230:Prostaglandin D2 / Q000096:biosynthesis* / Q000276:immunology* / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011720:Pyrazoles; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000378:metabolism; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D006827:Hydantoins; D007527:Isoenzymes; D054834:Lipocalins; D011720:Pyrazoles; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; D014157:Transcription Factors; C030669:BW 245C; D009195:Peroxidase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D000068579:Celecoxib; D015230:Prostaglandin D2; D007213:Indomethacin; C036293:prostaglandin D2 receptor