Cyclooxygenase-2-derived prostaglandin D(2) is 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 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.
Authors	M N Ajuebor, A Singh, J L Wallace
Journal	American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 279 Issue 1 Pg. G238-44 (Jul 2000) ISSN: 0193-1857 [Print] United States
PMID	10898767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors Hydantoins Isoenzymes Lipocalins Pyrazoles RNA, Messenger Receptors, Cytoplasmic and Nuclear Receptors, Immunologic Receptors, Prostaglandin Sulfonamides Transcription Factors BW 245C Peroxidase Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Intramolecular Oxidoreductases prostaglandin R2 D-isomerase Celecoxib Prostaglandin D2 Indomethacin prostaglandin D2 receptor
Topics	Animals Blotting, Western Celecoxib Colitis (enzymology, immunology, pathology) Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors (pharmacology) Disease Models, Animal Gene Expression Regulation, Enzymologic (immunology) Hydantoins (pharmacology) Indomethacin (pharmacology) Intramolecular Oxidoreductases (genetics, metabolism) Isoenzymes (genetics, metabolism) Lipocalins Male Necrosis Neutrophils (immunology) Peroxidase (metabolism) Peroxisomes (enzymology) Prostaglandin D2 (biosynthesis, immunology, pharmacology) Prostaglandin-Endoperoxide Synthases (genetics, metabolism) Pyrazoles RNA, Messenger (analysis) Rats Rats, Wistar Receptors, Cytoplasmic and Nuclear (analysis, metabolism) Receptors, Immunologic Receptors, Prostaglandin (agonists, metabolism) Sulfonamides (pharmacology) Transcription Factors (analysis, metabolism)

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