title: Identification of novel cyclooxygenase-2-dependent genes in Helicobacter pylori infection in vivo.
abstract: BACKGROUND
  Helicobacter pylori is 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 the Cox-2 gene is up-regulated in the gastric mucosa during H. pylori infection 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 an in vivo model, thereby identifying potential targets for the study of the role of Cox- 2 in H. pylori pathogenesis 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) after H. pylori infection. H. pylori infection 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 of H. pylori infection. 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.
  
  
  CONCLUSIONS
  This study has identified a panel of novel Cox-2 dependent genes influenced under both normal and the inflammatory conditions induced by H. pylori infection. These data provide important new links between Cox-2 and inflammatory processes, epithelial repair and integrity.
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany. AWalduck@unimelb.edu.au
authors.forename: Anna K
authors.initials: AK
authors.lastname: Walduck
authors.forename: Matthias
authors.initials: M
authors.lastname: Weber
authors.forename: Christian
authors.initials: C
authors.lastname: Wunder
authors.forename: Stefan
authors.initials: S
authors.lastname: Juettner
authors.forename: Manfred
authors.initials: M
authors.lastname: Stolte
authors.forename: Michael
authors.initials: M
authors.lastname: Vieth
authors.forename: Bertram
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Meyer
authors.forename: Michael
authors.initials: M
authors.lastname: Naumann
authors.forename: Michael
authors.initials: M
authors.lastname: Hoecker