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-kappaB-mediated inflammatory response. The NF-kappaB 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-kappaB complex. The heat shock response can cause the dissociation of the IKK complex, composed of protein kinase subunits IKKalpha and IKKbeta and the regulatory unit NEMO, and inhibit the activation of NF-kappaB signaling. Suppression of immune signaling during cellular stress may be a useful feedback response for helping cells to survive tissue injury. Furthermore, IKKalpha and IKKbeta 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.
Salminen
Antero
A
Department of Neuroscience and Neurology, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. antero.salminen@uku.fi
Paimela
Tuomas
T
Suuronen
Tiina
T
Kaarniranta
Kai
K
D000818:Animals; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response; D051550:I-kappa B Kinase / Q000378:metabolism*; D007113:Immunity, Innate; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D016328:NF-kappa B; D051550:I-kappa B Kinase