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Activation of IB Kinase β and NF-B Is Essential for Helicobacter pylori-Induced Chronic Gastritis in Mongolian Gerbils

Division of Gastroenterology, Institute for Adult Diseases, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo 100-0005,¹ Department of Gastroenterology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655,² Institute of Medicinal Molecular Design, Inc., 5-24-5 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan³

Received 28 July 2007/ Returned for modification 30 August 2007/ Accepted 27 November 2007

The Mongolian gerbil model of Helicobacter pylori infection resembles human gastritis. In this study, we investigated the role of NF-B activation in H. pylori-infected gerbils. Activated macrophages were significantly increased in H. pylori-infected gastric mucosa and were identified as being important cells with potent activation of NF-B, which plays an important part in producing proinflammatory cytokines. Macrophage depletion by the administration of clodronate resulted in milder inflammation in gerbils infected with H. pylori. In macrophages, the inhibition of IB kinase β (IKKβ), which is a critical kinase for NF-B activation, resulted in lower proinflammatory cytokine expression caused by heat-killed H. pylori cells. Furthermore, treatment with IKKβ inhibitor resulted in milder inflammation in gerbils with H. pylori gastritis. Collectively, our data suggest that H. pylori-mediated gastric inflammation critically depends on the efficient recruitment and activation of macrophages, with sufficient NF-B activation.

Published ahead of print on 10 December 2007.

Editor: B. A. McCormick