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- Title
Osmotic stress blocks NF-κB-dependent inflammatory responses by inhibiting ubiquitination of IκB
- Authors
HuangFu, Wei-Chun; Matsumoto, Kunihiro; Ninomiya-Tsuji, Jun
- Abstract
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-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.
- Subjects
MACROPHAGES; BONE marrow; CYTOKINES; CHEMOKINES
- Publication
FEBS Letters, 2007, Vol 581, Issue 29, p5549
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2007.11.002