Cyclooxygenase-1 and -2 gene disruption potentiateTH1 polarization in response to helicobacter pylori

Abstract

Objectives We have demonstrated that COX-1 and COX-2 dis-ruption enhances H. pylori (Hp)-induced gastritis. This study aimedto determine whether this effect is through the potentiation of theTh1 response and/or compensatory production of leukotrienes (LTs).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 expression of gastric mucosalIL-12, IFN-g, IL-10 and IL-4 mRNA was determined by RT-PCR,and the levels of LTB4and LTC4proteins were detected by ELISA. Results In the presence of Hp infection, expression of IL-12, IFN-g, IL-10 and IL-4 mRNA was elevated in WT mice, but only IL-12and IFN-g mRNA expression were further increased in both COX-1-/- and COX-2-/- mice. Both LTB4and LTC4levels were increasedin Hp infected WT, COX-1-/- and COX-2-/- mice compared withtheir uninfected controls, but there was no further increase in LTB4and LTC4production in both COX-1-/- and COX-2-/- mice (table).Conclusion COX-1 and COX-2 disruption enhances Hp-inducedgastritis is associated with the potentiation of Th1 polarization, butnot with compensatory LT production.