Abstract
Background
Helicobacter pyloriis a crucial determining factor in the pathogenesis of benign and neoplastic gastric diseases. Cyclooxygenase-2 (Cox-2) is the inducible key enzyme of arachidonic acid metabolism and is a central mediator in inflammation and cancer. Expression of theCox-2gene is up-regulated in the gastric mucosa duringH. pyloriinfection but the pathobiological consequences of this enhanced Cox-2 expression are not yet characterized. The aim of this study was to identify novel genes down-stream of Cox-2 in anin vivomodel, thereby identifying potential targets for the study of the role of Cox- 2 inH. pyloripathogenesis and the initiation of pre- cancerous changes.
Results
Gene expression profiles in the gastric mucosa of mice treated with a specific Cox-2 inhibitor (NS398) or vehicle were analysed at different time points (6, 13 and 19 wk) afterH. pyloriinfection.H. pyloriinfection affected the expression of 385 genes over the experimental period, including regulators of gastric physiology, proliferation, apoptosis and mucosal defence. Under conditions of Cox-2 inhibition, 160 target genes were regulated as a result ofH. pyloriinfection. The Cox-2 dependent subset included those influencing gastric physiology (Gastrin, Galr1), epithelial barrier function (Tjp1, connexin45, Aqp5), inflammation (Icam1), apoptosis (Clu) and proliferation (Gdf3, Igf2). Treatment with NS398 alone caused differential expression of 140 genes, 97 of which were unique, indicating that these genes are regulated under conditions of basal Cox-2 expression.
Conclusion
This study has identified a panel of novel Cox-2 dependent genes influenced under both normal and the inflammatory conditions induced byH. pyloriinfection. These data provide important new links between Cox-2 and inflammatory processes, epithelial repair and integrity.
