Helicobacter pylori induces cyclooxygenase‐1 and cyclooxygenase‐2 expression in vascular endothelial cells

Abstract

Background: Helicobacter pylori induces cyclooxygenase activity in the stomach, although the COX isoform and cellular source are unclear. A potential source is the vascular endothelial cell, which plays a role in regulating mucosal blood flow and inflammatory cell infiltration. Methods: We examined the effect of four strains (toxigenic and non‐toxigenic) of H. pylori on COX isoform expression in vascular endothelial cells. Prostaglandin synthesis was measured by enzyme immunoassay and COX isozyme expression determined by Western blot and RT‐PCR. Gene induction was examined using 5′ deletion constructs of the COX‐1 and COX‐2 promoters coupled with luciferase. Results: All H. pylori strains induced prostaglandin generation and expression of both COX‐1 and COX‐2 in HUVEC, although this was most pronounced with the highly toxigenic strain H. pylori 60190. Treatment of the cells with selective COX inhibitors demonstrated that COX‐1 was predominantly responsible for the enhanced generation of prostacyclin induced by H. pylori 60190. Similar results were seen with H. pylori broth culture filtrates, suggesting that a secreted product was responsible. Induction of COX‐2 reflected both enhanced gene expression and stabilization of the mRNA. Conclusions: H. pylori increased both COX‐1 and COX‐2 activity in vascular endothelial cells. This increased generation of endothelial cell prostacyclin may play a role in modulating mucosal blood flow, platelet function and inflammatory cell infiltration in response to H. pylori infection. The regulation of COX‐1 at the transcriptional level by H. pylori described in this study is a novel finding and calls into question the traditional description of COX‐1 as a purely constitutive, housekeeping gene.