Ca2+/calmodulin-dependent kinase II contributes to inhibitor of nuclear factor-kappa B kinase complex activation in Helicobacter pylori infection

Helicobacter pylori, a class I carcinogen, induces a proinflammatory response by activating the transcription factor nuclear factor-kappa B (NF-B) in gastric epithelial cells. This inflammatory condition could lead to chronic gastritis, which is epidemiologically and biologically linked to the development of gastric cancer. So far, there exists no clear knowledge on how H. pylori induces the NF-B-mediated inflammatory response. In our study, we investigated the role of Ca2+/calmodulin-dependent kinase II (CAMKII), calmodulin, protein kinases C (PKCs) and the CARMA3-Bcl10-MALT1 (CBM) complex in conjunction with H. pylori-induced activation of NF-B via the inhibitor of nuclear factor-kappa B kinase (IKK) complex. We use specific inhibitors and/or RNA interference to assess the contribution of these components. Our results show that CAMKII and calmodulin contribute to IKK complex activation and thus to the induction of NF-B in response to H. pylori infection, but not in response to TNF-. Thus, our findings are specific for H. pylori infected cells. Neither the PKCs , , , nor the CBM complex itself is involved in the activation of NF-B by H. pylori. The contribution of CAMKII and calmodulin, but not PKCs/CBM to the induction of an inflammatory response by H. pylori infection augment the understanding of the molecular mechanism involved and provide potential new disease markers for the diagnosis of gastric inflammatory diseases including gastric cancer. What's new?Helicobacter pylori incites inflammation in gastric epithelial cells through NF-B activation, increasing the risk of gastric cancer. But missing links in the mechanism are yet to be described. Here, the authors show, for the first time, that CAMKII and calmodulin participate in H. pylori-induced activation of NF-B. Constitutive or aberrant NF-B activity promotes tumor survival, and CAMKII has been implicated in the regulation of cancer cell growth. Thus, this study offers the possibility that CAMKII and calmodulin are potential biomarkers and are of clinical importance for the diagnosis of gastric diseases, including gastric cancer.