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Roles of cyclooxygenase 2 and microsomal prostaglandin E synthase 1 in rat acid reflux oesophagitis.
Gut. 2006 Apr; 55(4):450-6.Gut

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.

Authors+Show Affiliations

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Abenoku, Osaka 545-8585, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16210398

Citation

Hayakawa, T, et al. "Roles of Cyclooxygenase 2 and Microsomal Prostaglandin E Synthase 1 in Rat Acid Reflux Oesophagitis." Gut, vol. 55, no. 4, 2006, pp. 450-6.
Hayakawa T, Fujiwara Y, Hamaguchi M, et al. Roles of cyclooxygenase 2 and microsomal prostaglandin E synthase 1 in rat acid reflux oesophagitis. Gut. 2006;55(4):450-6.
Hayakawa, T., Fujiwara, Y., Hamaguchi, M., Sugawa, T., Okuyama, M., Sasaki, E., Watanabe, T., Tominaga, K., Oshitani, N., Higuchi, K., & Arakawa, T. (2006). Roles of cyclooxygenase 2 and microsomal prostaglandin E synthase 1 in rat acid reflux oesophagitis. Gut, 55(4), 450-6.
Hayakawa T, et al. Roles of Cyclooxygenase 2 and Microsomal Prostaglandin E Synthase 1 in Rat Acid Reflux Oesophagitis. Gut. 2006;55(4):450-6. PubMed PMID: 16210398.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Roles of cyclooxygenase 2 and microsomal prostaglandin E synthase 1 in rat acid reflux oesophagitis. AU - Hayakawa,T, AU - Fujiwara,Y, AU - Hamaguchi,M, AU - Sugawa,T, AU - Okuyama,M, AU - Sasaki,E, AU - Watanabe,T, AU - Tominaga,K, AU - Oshitani,N, AU - Higuchi,K, AU - Arakawa,T, Y1 - 2005/10/06/ PY - 2005/10/8/pubmed PY - 2006/5/4/medline PY - 2005/10/8/entrez SP - 450 EP - 6 JF - Gut JO - Gut VL - 55 IS - 4 N2 - 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. SN - 0017-5749 UR - https://www.unboundmedicine.com/medline/citation/16210398/Roles_of_cyclooxygenase_2_and_microsomal_prostaglandin_E_synthase_1_in_rat_acid_reflux_oesophagitis_ L2 - http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=16210398 DB - PRIME DP - Unbound Medicine ER -