title: 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.
authors.affiliation: Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: HuangFu
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Jun
authors.initials: J
authors.lastname: Ninomiya-Tsuji
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009997:Osmotic Pressure; D015398:Signal Transduction; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D020672:I-kappa B Proteins; D007375:Interleukin-1; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D051550:I-kappa B Kinase