<i>Helicobacter pylori</i>Induces IκB Kinase α Nuclear Translocation and Chemokine Production in Gastric Epithelial Cells

<jats:title>ABSTRACT</jats:title><jats:p>NF-κB is an important transcriptional factor that is involved in multiple cellular responses, such as inflammation and antiapoptosis. IκB kinase α (IKKα) and IKKβ, which are critical regulators of NF-κB activity, possess various mechanisms for NF-κB activation. This variability in NF-κB signaling may be associated with distinct inflammatory responses in specific cell types. The gastric pathogen<jats:italic>Helicobacter pylori</jats:italic>is known to activate NF-κB. However, the role of IKK in<jats:italic>H. pylori</jats:italic>infection remains unclear. In this report, we show that<jats:italic>H. pylori</jats:italic>activates both IKKα and IKKβ in gastric cancer cells and enhances NF-κB signaling in distinct manners. We found that IKKβ acted as an IκBα kinase during<jats:italic>H. pylori</jats:italic>infection, whereas IKKα did not.<jats:italic>H. pylori</jats:italic>induced IKKα nuclear translocation in time-, multiplicity of infection-, and<jats:italic>cag</jats:italic>pathogenicity island-dependent manners. In contrast, p100 processing, which is a known IKKα activity induced by several cytokines, was not induced by<jats:italic>H. pylori</jats:italic>. Both IKKs were responsible for chemokine secretion by infected cells. However, the antiapoptotic effect of<jats:italic>H. pylori</jats:italic>was merely transduced by IKKβ. 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<jats:italic>H. pylori</jats:italic>activates NF-κB via both IKKα and IKKβ using distinct mechanisms. IKKα nuclear translocation induced by<jats:italic>H. pylori</jats:italic>is indispensable for appropriate inflammatory responses but not for antiapoptosis, which suggests a critical role for IKKα in gastritis development.</jats:p>