Roles of cyclooxygenase-2 and prostaglandin E receptors in gastric mucosal defense in Helicobacter pylori-infected mice

Abstract.

Background/Aim:

Helicobacter pylori (H. pylori) induces cyclooxygenase-2 (COX-2) expression. The aim of this study was to assess the roles of COX-2 and PGE₂ receptors (EPs) in gastric defense in H. pylori-infected mice.

Methods:

Gastric lesions were induced by oral administration of 0.15 N HCl in 60 % ethanol (HCl/EtOH) to mice infected with H. pylori, and macroscopically evaluated 30 min later. Mice were administered NS-398 (COX-2 selective inhibitor) concomitantly with selective EP agonists 4 hours before HCl/EtOH challenge.

Results:

H. pylori infection prevented the gastric damage induced by HCl/EtOH, and this protective effect was abolished by NS-398. Selective agonists of EP1, EP2, and EP4, but not the EP3 agonist, reversed the inhibitory effect of NS-398 on prevention of damage by H. pylori infection. The EP4 agonist and EP2/EP4 agonists inhibited the increase in TNF-α mRNA expression and neutrophilic infiltration caused by NS-398, respectively.

Conclusion:

COX-2-derived PGE₂ may play an important role in resistance to HCl/EtOH damage in H. pylori-infected mice by activating EP1, EP2, and EP4.