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 investigat...

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Bibliographic Details
Published in:American journal of physiology: Gastrointestinal and liver physiology 2000-07, Vol.279 (1), p.G238-G244
Main Authors: Ajuebor, M N, Singh, A, Wallace, J L
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Celecoxib
Colitis - enzymology
Colitis - immunology
Colitis - pathology
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors - pharmacology
Disease Models, Animal
Gene Expression Regulation, Enzymologic - immunology
Hydantoins - pharmacology
Indomethacin - pharmacology
Intramolecular Oxidoreductases - genetics
Intramolecular Oxidoreductases - metabolism
Isoenzymes - genetics
Isoenzymes - metabolism
Lipocalins
Male
Necrosis
Neutrophils - immunology
Peroxidase - metabolism
Peroxisomes - enzymology
Prostaglandin D2 - biosynthesis
Prostaglandin D2 - immunology
Prostaglandin D2 - pharmacology
Prostaglandin-Endoperoxide Synthases - genetics
Prostaglandin-Endoperoxide Synthases - metabolism
Pyrazoles
Rats
Rats, Wistar
Receptors, Cytoplasmic and Nuclear - analysis
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Immunologic
Receptors, Prostaglandin - agonists
Receptors, Prostaglandin - metabolism
RNA, Messenger - analysis
Sulfonamides - pharmacology
Transcription Factors - analysis
Transcription Factors - metabolism
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Summary: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.
ISSN:0193-1857