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

Am J Physiol Gastrointest Liver Physiol. 2000 Jul;279(1):G238-44. doi: 10.1152/ajpgi.2000.279.1.G238.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Receptors, Cytoplasmic and Nuclear / analysis
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Immunologic*
  • Receptors, Prostaglandin / agonists
  • Receptors, Prostaglandin / metabolism
  • Sulfonamides / pharmacology
  • Transcription Factors / analysis
  • Transcription Factors / metabolism

Substances

  • 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