TY - JOUR
T1 - Identification of novel Cyclooxygenase-2-dependent genes in Helicobacter pylori infection in vivo
AU - Walduck, Anna K.
AU - Weber, Matthias
AU - Wunder, Christian
AU - Juettner, Stefan
AU - Vieth, Michael
AU - Wiedenmann, Bertram
AU - Meyer, Thomas F.
AU - Naumann, Michael
AU - Hoecker, Michael
N1 - Funding Information:
The authors wish to thank Marina Drabkina, Jörg Angermann, Frauke Sch-reiber, Dagmar Frahm, Kirsten Hoffmann and Annette Dietrich for excellent technical assistance. We are indebted to Yevhen Vainshtein and Hans Mollenkopf for their contributions to the design of the mouse oligonucleotide array and Claudia Scheppers for maintenance of the Resolver database. The support and co-operation of Götz Frommer and Andreas Rhülman of Agilent Technologies, and proofreading of the manuscript by Lesley Ogilvie are also gratefully acknowledged. This work was funded by the Max-Planck Society Tandem Project 'Significance of Helicobacter pylori induced COX-2 gene expression'.
PY - 2009/3/24
Y1 - 2009/3/24
N2 - BackgroundHelicobacter 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.ResultsGene 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.ConclusionThis 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.
AB - BackgroundHelicobacter 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.ResultsGene 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.ConclusionThis 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.
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U2 - 10.1186/1476-4598-8-22
DO - 10.1186/1476-4598-8-22
M3 - Article
AN - SCOPUS:65449178116
SN - 1476-4598
VL - 8
JO - Molecular Cancer
JF - Molecular Cancer
M1 - 22
ER -
