Effects of cyclooxygenase-1 and -2 gene disruption onhelicobacter pylori-induced inflammation, apoptosisand proliferation

Abstract

Objectives To investigate the effects of COX-1 and COX-2 dis-ruption on H. pylori (Hp)-induced gastric inflammation, apoptosisand proliferation.Methods Hp strain TN2 was inoculated into the stomachs of COX-1 and COX-2 deficient homozygous (COX-1-/-, COX-2-/-) and con-geneic wild-type (WT) mice. Mice were sacrificed 24 wks later (n =8–10 mice/group). WT, COX-1-/- and COX-2-/- mice without Hpinoculation were used as controls.The density of Hp colonization, theseverity of chronic gastric inflammation, apoptosis and proliferationof gastric epithelial cells, TNF-a and PGE2were determined.Results There was no significant difference in the density of Hpcolonization between WT and COX-/- mice. Hp-induced gastritis wasmarkedly more severe in both COX-1-/- and COX-2-/- mice. Hp infec-tion increased apoptosis in WT (4.7-fold) and COX-1-/- (4.8-fold)mice, compared with their uninfected controls. Apoptosis was furtherincreased in Hp infected COX-2-/- mice compared with Hp infectedWT and COX-1-/- mice although the difference was not statisticallysignificance. Cell proliferation was increased in WT (2.3-fold) andCOX-1-/- (2.4-fold) mice, but not in COX-2-/- mice in the presenceof Hp infection. Hp infection increased expression of gastric mucosalTNF-a mRNA (4.4-fold) in WT mice, and further increased TNF-amRNA expression in COX-1-/- (1.8-fold vs.WT) and COX-2-/- (2.0-fold vs. WT) mice. Hp infection increased gastric PGE2level in WT(1.6-fold) and COX-2-/- (1.4-fold) mice. PGE2was detected at verylow levels in COX-1-/- mice with or without Hp infection.Conclusion In a 24-wk Hp colonization study model, COX-1 andCOX-2 deficiency enhances Hp-induced gastritis, probably via TNF-a expression, but has no significant effect on Hp-induced apoptosis.Deficiency of COX-2, but not COX-1, inhibits Hp-induced cell proliferation.