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- Title
Sensitization of IFN-gamma Jak-STAT signaling during macrophage activation.
- Authors
Hu, Xiaoyu; Herrero, Carmen; Li, Wai-Ping; Antoniv, Taras T; Falck-Pedersen, Erik; Koch, Alisa E; Woods, James M; Haines, G Kenneth; Ivashkiv, Lionel B
- Abstract
A general paradigm in signal transduction is ligand-induced feedback inhibition and the desensitization of signaling. We found that subthreshold concentrations of interferon-gamma (IFN-gamma), which did not activate macrophages, increased their sensitivity to subsequent IFN-gamma stimulation; this resulted in increased signal transducer and activator of transcription 1 (STAT1) activation and increased IFN-gamma#150;dependent gene activation. Sensitization of IFN-gamma signaling was mediated by the induction of STAT1 expression by low doses of IFN-gamma that did not effectively induce feedback inhibition. IFN-gamma signaling was sensitized in vivo after IFN-gamma injection, and STAT1 expression was increased after injection of lipopolysaccharide and in rheumatoid arthritis synovial cells. These results identify a mechanism that sensitizes macrophages to low concentrations of IFN-gamma and regulates IFN-gamma responses in acute and chronic inflammation.
- Publication
Nature immunology, 2002, Vol 3, Issue 9, p859
- ISSN
1529-2908
- Publication type
Journal Article
- DOI
10.1038/ni828