Role of IkB Kinase and Heat Shock Protein 90 Complex in Inflammatory Responses to Bacterial Infection (pp. 135-152)
Authors: (Jung Mogg Kim, Department of Microbiology, Hanyang University College of Medicine, Seoul, South Korea)
Abstract: The IκB kinase (IKK) is a key enzyme complex that is associated with cellular responses to bacterial infection. The IKK is an important component of the upstream NF-κB signal transduction cascade that controls inflammatory processes in the human intestine. NF-B dimers are stored in the cytoplasm in an inactive state by inhibitory proteins called IBs, in which the IKK directly phosphorylates IB. This phosphorylation results in the dissociation of IκBs from NF-κB. The IKK complex contains three subunits: two catalytic subunits, IKK- and IKK-, and a regulatory subunit, IKK-. IKK- and IKK- are essential for IB phosphorylation, and IKK- forms a tetrameric scaffold that can assemble two kinase dimers which facilitates trans-autophosphorylation. Heat shock protein 90 (Hsp90) has been found to associate stoichiometrically with the IKK complex, which may contribute to the stabilization, activation, and/or shuttling of IKKs to the plasma membrane.
Helicobacter pylori is a pathogen that has an important role in the pathogenesis of chronic gastritis, peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Enterotoxigenic Bacteroides fragilis (ETBF) is associated with colitis and colorectal cancer, in which a definite virulence factor for these diseases is B. fragilis enterotoxin (BFT). Bacterial infection such as ETBF and H. pylori induces a signaling cascade including IKK-NF-B activation and interleukin (IL)-8
secretion. This signaling is predicted to lead to mucosal transmigration of neutrophils and inflammation. We discuss the regulation of IKK and Hsp90 complex in inflammatory responses to bacterial infection in the chapter.