Roles of cyclooxygenase 2 and microsomal prostaglandin E synthase 1 in rat acid reflux oesophagitis

T. Hayakawa; Fujiwara, Y.; Hamaguchi, M.; Sugawa, T.; Okuyama, M.; Sasaki, E.; Watanabe, T.; Tominaga, K.; Oshitani, N.; Oshitani, K.; Higuchi, K.; Arakawa, T.
April 2006
Gut;Apr2006, Vol. 55 Issue 4, p450
Academic Journal
Background: Although prostaglondin 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 reflex oesophagitis and the effects of COX-2 inhibitors on the severity of oesophagitis. Methods: Acid reflux aesophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and wrapping the duodenum near the pylorus. Rats were killed an day 3 (acute phase) or day 21 (chronic phase) after induction of aesophagitis. 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 bath days 3 and 21. Epithelial proliferation was significantly increased in the basal layer an day 21. Inflammatory cells and epithelial cells of the basal layer exhibited reactions far EP4 in oesophagitis. Conclusion: PGE2 derived from COX-2 and mPGES-1 plays a significant role in the pathogenesis of chronic acid reflex oesophagitis, and possibly in basal hyperplasia and persistent inflammatory cell infiltration.


Related Articles

  • COX-2 mRNA expression is significantly increased in acid-exposed compared to nonexposed squamous epithelium in gastroesophageal reflux disease. Lurje, Georg; Vallbohmer, Daniel; Collet, Peter H.; Huan Xi; Baldus, Stephan E.; Brabender, Jan; Metzger, Ralf; Heitmann, Michaela; Neiss, Susanne; Drebber, Ute; Holscher, Arnulf H.; Schneider, Paul M.; Xi, Huan // Journal of Gastrointestinal Surgery;Sep2007, Vol. 11 Issue 9, p1105 

    Background: Little is known about the role of cyclooxygenase (COX)-2 in gastroesophageal reflux disease (GERD) and the development of Barrett's metaplasia. The objectives of this study were to further analyze COX-2 mRNA expression in patients with GERD compared to Barrett's...

  • Specialized Columnar Epithelium of the Esophagogastric Junction: Prevalence and Associations. Voutilainen, Markku; Färkkilä, Martti; Juhola, Matti; Nuorva, Kyösti; Mauranen, Kari; Mäntynen, Timo; Kunnamo, Ilkka; Mecklin, Jukka-Pekka; Sipponen, Pentti // American Journal of Gastroenterology;Apr1999, Vol. 94 Issue 4, p913 

    OBJECTIVES: In Barrett's esophagus (BE) normal squamous esophageal epithelium is replaced by specialized columnar epithelium (SCE). BE is related to astroesophageal reflux disease (GERD) and is a risk factor for esophageal adenocarcinoma. SCE is detected also at normal-appearing esophagogastric...

  • COX-2 CA-Haplotype Is a Risk Factor for the Development of Esophageal Adenocarcinoma. Moons, Leon M. G.; Kuipers, Ernst J.; Rygiel, Agnieszka M.; Groothuismink, Anthonie Z. M.; Geldof, Han; Bode, Willem A.; Krishnadath, Kausilia K.; Bergman, Jacques J. G. H. M.; van Vliet, Arnoud H. M.; Siersema, Peter D.; Kusters, Johannes G. // American Journal of Gastroenterology;Nov2007, Vol. 102 Issue 11, p2373 

    BACKGROUND: Neoplastic progression of BE towards EAC is associated with increased expression of COX-2. Increased COX-2 expression and enzyme activity is linked to the COX-2 CA haplotype, which consists of two gene polymorphisms in the COX-2 promoter. AIM: To study the impact of COX-2 haplotypes...

  • Oesophageal mucosal barrier: a key factor in the pathophysiology of non-erosive reflux disease (NERD) and a potential target for treatment. Woodland, Philip; Sifrim, Daniel // Gut;May2014, Vol. 63 Issue 5, p705 

    The authors expresses their views concerning on the factors of non-erosive reflux disease (NERD) in the pathophysiology and its potential treatment for reflux disease. One of the author mentions the significance of trans-epithelial electrical resistance (TEER) in oesophageal mucosal barrier...

  • Tryptase Staining of Mast Cells May Differentiate Eosinophilic Esophagitis from Gastroesophageal Reflux Disease. Dellon, Evan S.; Xiaoxin Chen; Miller, C. Ryan; Fritchie, Karen J.; Rubinas, Tara C.; Woosley, John T.; Shaheen, Nicholas J. // American Journal of Gastroenterology;Feb2011, Vol. 106 Issue 2, p264 

    OBJECTIVES:Mast cells may contribute to the pathogenesis of eosinophilic esophagitis (EoE), but their role in diagnosis is unknown. Our aim was to determine whether tryptase staining of esophageal mast cells differentiates EoE from gastroesophageal reflux disease (GERD) and has utility for...

  • Pulmonary and Cardiorenal Cyclooxygenase-1 (COX-1), -2 (COX-2), and Microsomal Prostaglandin E Synthase-1 (mPGES-1) and -2 (mPGES-2) Expression in a Hypertension Model. Radi, Zaher A.; Ostroski, Robert // Mediators of Inflammation;2/1/2007, Vol. 2007 Issue 1, Special section p1 

    Hypertensive mice that express the human renin and angiotensinogen genes are used as a model for human hypertension because they develop hypertension secondary to increased renin-angiotensin system activity. Our study investigated the cellular localization and distribution of COX-l, COX-2,...

  • Acid reflux impacts quality of life.  // Chain Drug Review;2/13/2012, Vol. 34 Issue 3, p31 

    The article informs that cases of chronic gastroesophageal reflux disease have increased in the U.S. over the past decade.

  • Is It Really Heartburn? Tennesen, Michael // Prevention;Mar2002, Vol. 54 Issue 3, p112 

    Focuses on gastro-esophageal reflux disease (GERD) with information on its symptoms, the potential threat of esophageal cancer, and treatments, including medication and diet changes. INSETS: WHAT ABOUT SURGERY?;HOW MANY CHEESEBURGERS DOES IT TAKE TO GIVE YOU HEARTBURN?.

  • Erratum: Use of a Simple Symptom Questionnaire to Predict Barrett's Esophagus in Patients With Symptoms of Gastroesophageal Reflux. Gerson, Lauren B; Edson, Robert; Lavori, Philips W; Triadafilopoulos, George // American Journal of Gastroenterology;May2014, Vol. 109 Issue 5, p781 

    A correction to the article "Use of a Simple Symptom Questionnaire to Predict Barrett's Esophagus in Patients With Symptoms of Gastroesophageal Reflux" that was published in the previous issue is presented.


Read the Article


Sign out of this library

Other Topics