Sensitization of IFN-γ Jak-STAT signaling during macrophage activation
- 12 August 2002
- journal article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 3 (9), 859-866
- https://doi.org/10.1038/ni828
Abstract
A general paradigm in signal transduction is ligand-induced feedback inhibition and the desensitization of signaling. We found that subthreshold concentrations of interferon-γ (IFN-γ), which did not activate macrophages, increased their sensitivity to subsequent IFN-γ stimulation; this resulted in increased signal transducer and activator of transcription 1 (STAT1) activation and increased IFN-γ–dependent gene activation. Sensitization of IFN-γ signaling was mediated by the induction of STAT1 expression by low doses of IFN-γ that did not effectively induce feedback inhibition. IFN-γ signaling was sensitized in vivo after IFN-γ 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-γ and regulates IFN-γ responses in acute and chronic inflammation.Keywords
This publication has 47 references indexed in Scilit:
- SOCS Proteins: Negative Regulators of Cytokine SignalingThe International Journal of Cell Cloning, 2001
- IFN-γ–dependent transcription of MHC class II IA is impaired in macrophages from aged miceJCI Insight, 2001
- Antinuclear Autoantibodies and Lupus Nephritis in Transgenic Mice Expressing Interferon γ in the EpidermisThe Journal of Experimental Medicine, 1997
- CELLULAR RESPONSES TO INTERFERON-γAnnual Review of Immunology, 1997
- Targeted Disruption of the Stat1 Gene in Mice Reveals Unexpected Physiologic Specificity in the JAK–STAT Signaling PathwayCell, 1996
- Functional Role of Type I and Type II Interferons in Antiviral DefenseScience, 1994
- Macrophage inflammatory protein-1 alpha. A novel chemotactic cytokine for macrophages in rheumatoid arthritis.JCI Insight, 1994
- Expression of interleukin-1 and interleukin-1 receptor antagonist by human rheumatoid synovial tissue macrophagesClinical Immunology and Immunopathology, 1992
- Loss of pancreatic islet tolerance induced by β-cell expression of interferon-γNature, 1990
- The american rheumatism association 1987 revised criteria for the classification of rheumatoid arthritisArthritis & Rheumatism, 1988