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Osmotic stress blocks NF‐κB‐dependent inflammatory responses by inhibiting ubiquitination of IκB
Author(s) -
HuangFu Wei-Chun,
Matsumoto Kunihiro,
Ninomiya-Tsuji Jun
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.11.002
Subject(s) - ubiquitin , osmotic shock , chemokine , microbiology and biotechnology , inflammation , phosphorylation , nf κb , tonicity , signal transduction , cytokine , p38 mitogen activated protein kinases , chemistry , biology , immunology , biochemistry , protein kinase a , gene
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‐κB pathway, a central signaling pathway in inflammation. We unexpectedly found that osmotic stress could activate IκBα kinase but did not activate NF‐κB. Osmotic stress‐induced phosphorylated IκBα was not ubiquitinated, and osmotic stress inhibited interleukin 1‐induced ubiquitination of IκBα and ultimately blocked expression of cytokine/chemokines. Thus, blockage of IκBα ubiquitination is likely to be a major mechanism for inhibition of inflammation by hypertonic conditions.