title: Roles of cyclooxygenase 2 and microsomal prostaglandin E synthase 1 in rat acid reflux oesophagitis.
abstract: BACKGROUND
  Although prostaglandin E2 (PGE2), cyclooxygenase 2 (COX-2), and microsomal prostaglandin E synthase 1 (mPGES-1) are known to play a role in various inflammatory events, their roles in the pathogenesis of gastro-oesophageal reflux disease are not known.
  
  
  OBJECTIVE
  We examined the dynamics of COX-1, COX-2, mPGES-1, mPGES-2, cytosolic PGES (cPGES), and PGE2 synthetic activity in rat acid reflux oesophagitis and the effects of COX-2 inhibitors on the severity of oesophagitis.
  
  
  METHODS
  Acid reflux oesophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and wrapping the duodenum near the pylorus. Rats were killed on day 3 (acute phase) or day 21 (chronic phase) after induction of oesophagitis.
  
  
  RESULTS
  Expression of COX-2 and mPGES-1 was markedly increased in oesophagitis while modest changes in COX-1, cPGES, and mPGES-2 expression were observed. COX-2 and mPGES-1 were colocalised in epithelial cells of the basal layer, as well as inflammatory and mesenchymal cells in the lamina propria and submucosa. COX-2 inhibitors significantly reduced the severity of chronic oesophagitis but did not affect acute oesophageal lesions. COX-2 inhibitors significantly inhibited the increase in PGE2 synthesis in oesophageal lesions on both days 3 and 21. Epithelial proliferation was significantly increased in the basal layer on day 21. Inflammatory cells and epithelial cells of the basal layer exhibited reactions for EP4 in oesophagitis.
  
  
  CONCLUSIONS
  PGE2 derived from COX-2 and mPGES-1 plays a significant role in the pathogenesis of chronic acid reflux oesophagitis, and possibly in basal hyperplasia and persistent inflammatory cell infiltration.
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Abenoku, Osaka 545-8585, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: M
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Sugawa
authors.forename: M
authors.initials: M
authors.lastname: Okuyama
authors.forename: E
authors.initials: E
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Tominaga
authors.forename: N
authors.initials: N
authors.lastname: Oshitani
authors.forename: K
authors.initials: K
authors.lastname: Higuchi
authors.forename: T
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000818:Animals; D000068579:Celecoxib; D002455:Cell Division / Q000502:physiology; D002908:Chronic Disease; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D015232:Dinoprostone / Q000096:biosynthesis; D004847:Epithelial Cells / Q000502:physiology; D004942:Esophagitis, Peptic / Q000201:enzymology* / Q000503:physiopathology; D004947:Esophagus / Q000201:enzymology / Q000503:physiopathology; D007150:Immunohistochemistry / Q000379:methods; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D000071876:Prostaglandin-E Synthases; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018078:Receptors, Prostaglandin E / Q000032:analysis; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; C545652:Ptger4 protein, rat; D011720:Pyrazoles; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D000068579:Celecoxib; D015232:Dinoprostone; C012655:nimesulide