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

ABSTRACT The Mongolian gerbil model of Helicobacter pylori infection resembles human gastritis. In this study, we investigated the role of NF-κB 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-κB, 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 IκB kinase β (IKKβ), which is a critical kinase for NF-κB 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-κB activation.