Innate immunity meets with cellular stress at the IKK complex: Regulation of the IKK complex by HSP70 and HSP90

Several research models have shown that if cellular stress induces the heat shock response then this will suppress the NF-kappa B-mediated inflammatory response. The NF-kappa B signaling pathway mediates both stress signals and innate immunity signals. Heat shock proteins HSP70 and HSP90 regulate several signaling cascades to maintain cellular homeostasis. Recent studies have revealed that HSP70 and HSP90 proteins regulate the function of the IKK complex which is the major activator of the NF-kappa B complex. The heat shock response can cause the dissociation of the IKK complex, composed of protein kinase subunits IKK alpha and IKK beta and the regulatory unit NEMO, and inhibit the activation of NF-kappa B signaling. Suppression of immune signaling during cellular stress may be a useful feedback response for helping cells to survive tissue injury. Furthermore, IKK alpha and IKK beta kinases are important activators of tumorigenesis and hence the inhibition of long-term activation of the IKK complex by HSP70 and HSP90 proteins may prevent cancer development during chronic inflammation. (C) 2008 Elsevier B.V. All rights reserved.