Helicobacter pylori induces IκB kinase at nuclear translocation and chemokine production in gastric epithelial cells

NF-kappa B is an important transcriptional factor that is involved in multiple cellular responses, such as inflammation and antiapoptosis. I kappa B kinase alpha (IKK alpha) and IKK beta, which are critical regulators of NF-kappa B activity, possess various mechanisms for NF-kappa B activation. This variability in NF-kappa B signaling may be associated with distinct inflammatory responses in specific cell types. The gastric pathogen Helicobacter pylori is known to activate NF-kappa B. However, the role of IKK in H. pylori infection remains unclear. In this report, we show that H. pylori activates both IKK alpha and IKK beta in gastric cancer cells and enhances NF-kappa B signaling in distinct manners. We found that IKK beta acted as an I kappa B alpha kinase during H. pylori infection, whereas IKK alpha did not. H. pylori induced IKK alpha nuclear translocation in time-, multiplicity of infection-, and cag pathogenicity island-dependent manners. In contrast, p100 processing, which is a known IKK alpha activity induced by several cytokines, was not induced by H. pylori. Both IKKs were responsible for chemokine secretion by infected cells. However, the antiapoptotic effect of H. pylori was merely transduced by IKK beta. Microarray analysis and real-time PCR indicated that both IKKs were involved in the transcriptional activation of genes associated with inflammation, antiapoptosis, and signal transduction. Our results indicate that H. pylori activates NF-kappa B via both IKK alpha and IKK beta using distinct mechanisms. IKK alpha nuclear translocation induced by H. pylori is indispensable for appropriate inflammatory responses but not for antiapoptosis, which suggests a critical role for IKK alpha in gastritis development.