Identification of novel Cyclooxygenase-2-dependent genes in Helicobacter pylori infection in vivo

doi:10.1186/1476-4598-8-22

Molecular Cancer

Volume 8

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Walduck AK
Weber M
Wunder C
Juettner S
Stolte M
Vieth M
Wiedenmann B
Meyer TF
Naumann M
Hoecker M

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Walduck AK
Weber M
Wunder C
Juettner S
Stolte M
Vieth M
Wiedenmann B
Meyer TF
Naumann M
Hoecker M
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Research

Identification of novel Cyclooxygenase-2-dependent genes in Helicobacter pylori infection in vivo

Anna K Walduck¹^,2^* , Matthias Weber¹^* , Christian Wunder¹^* , Stefan Juettner¹^,3 , Manfred Stolte⁴ , Michael Vieth⁴ , Bertram Wiedenmann³ , Thomas F Meyer¹ , Michael Naumann⁵^* and Michael Hoecker³^*

¹Department of Molecular Biology, Max Planck Institute for Infection Biology, Schumanstrasse 21/22 10117 Berlin, Germany

²Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC, 3010 Australia

³Department of Hepatology, Gastroenterology, Charité Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany

⁴Institute of Pathology, Klinikum Bayreuth, Preuschwitzer Strasse 101, 95445 Bayreuth, Germany

⁵Institute for Experimental and Internal Medicine, Faculty of Medicine, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany

author email corresponding author email* Contributed equally

Molecular Cancer 2009, 8:22doi:10.1186/1476-4598-8-22


Published:	24 March 2009

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.

Conclusion

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.