Osmotic stress blocks NF-κB-dependent in inflammatory responses by inhibiting ubiquitination of IκB

The inhibitory effects of hypertonic conditions on immune responses have been described in clinical studies; however, the molecular mechanism underlying this phenomenon has yet to be de. fined. Here we investigate osmotic stress-mediated modification of the NF-kappa B pathway, a central signaling pathway in inflammation. We unexpectedly found that osmotic stress could activate I kappa B alpha kinase but did not activate NF-kappa B. Osmotic stress-induced phosphorylated I kappa B alpha was not ubiquitinated, and osmotic stress inhibited interleukin 1-induced ubiquitination of I kappa B alpha and ultimately blocked expression of cytokine/chemokines. Thus, blockage of I kappa B alpha ubiquitination is likely to be a major mechanism for inhibition of inflammation by hypertonic conditions. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.