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Osmotic stress blocks NF-kappaB-dependent inflammatory responses by inhibiting ubiquitination of IkappaB.

ABSTRACT: 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 defined. Here we investigate osmotic stress-mediated modification of the NF-kappaB pathway, a central signaling pathway in inflammation. We unexpectedly found that osmotic stress could activate IkappaBalpha kinase but did not activate NF-kappaB. Osmotic stress-induced phosphorylated IkappaBalpha was not ubiquitinated, and osmotic stress inhibited interleukin 1-induced ubiquitination of IkappaBalpha and ultimately blocked expression of cytokine/chemokines. Thus, blockage of IkappaBalpha ubiquitination is likely to be a major mechanism for inhibition of inflammation by hypertonic conditions.

SUBMITTER: HuangFu WC

PROVIDER: S-EPMC2170878 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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Osmotic stress blocks NF-kappaB-dependent inflammatory responses by inhibiting ubiquitination of IkappaB.

HuangFu Wei-Chun WC Matsumoto Kunihiro K Ninomiya-Tsuji Jun J

FEBS letters 20071113 29

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 defined. Here we investigate osmotic stress-mediated modification of the NF-kappaB pathway, a central signaling pathway in inflammation. We unexpectedly found that osmotic stress could activate IkappaBalpha kinase but did not activate NF-kappaB. Osmotic stress-induced phosphorylated IkappaBalpha was not ubiquitinate ...[more]

PMID: 17997988

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