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Roles of cyclooxygenase 2 and microsomal prostaglandin E synthase 1 in rat acid reflux oesophagitis
  1. T Hayakawa,
  2. Y Fujiwara,
  3. M Hamaguchi,
  4. T Sugawa,
  5. M Okuyama,
  6. E Sasaki,
  7. T Watanabe,
  8. K Tominaga,
  9. N Oshitani,
  10. K Higuchi,
  11. T Arakawa
  1. Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Osaka, Japan
  1. Correspondence to:
    Dr Y Fujiwara
    Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi Abenoku, Osaka 545-8585, Japan; yasu{at}med.osaka-cu.ac.jp

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.

Aims: 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.

Conclusion: 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.

  • PG, prostaglandin
  • COX, cyclooxygenase
  • mPGES, microsomal prostaglandin E synthase
  • cPGES, cytosolic prostaglandin E synthase
  • GORD, gastro-oesophageal reflux disease
  • PCNA, proliferating cell nuclear antigen
  • RT-PCR, reverse transcription-polymerase chain reaction
  • GAPDH, glyceraldehyde-3-phosphate dehydrogenase
  • IL-1β, interleukin 1β
  • TNF-α, tumour necrosis factor α
  • cyclooxygenase 2
  • microsomal prostaglandin E synthesis 1
  • prostaglandin E2
  • cyclooxygenase 2 inhibitors
  • reflux oesophagitis

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Footnotes

  • Published online first 6 October 2005

  • Conflict of interest: None declared.

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