Negative regulation of interleukin-12 signaling by suppressor of cytokine signaling-1
- Author(s)
- Eyles, JL; Metcalf, D; Grusby, MJ; Hilton, DJ; Starr, R;
- Details
- Publication Year 2002-11-15,Volume 277,Issue #46,Page 43735-43740
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Publication Type
- Journal Article
- Abstract
- Suppressor of cytokine signaling-1 (SOCS-1) is an inhibitory protein that regulates responses to cytokines. Previously, we have shown SOCS-1 to be a key inhibitor of interferon gamma (IFNgamma). Recent data suggest that SOCS-1 may regulate other cytokines in vivo, in addition to IFNgamma. Uncontrolled responses to interleukin-12 (IL-12), an inflammatory cytokine, could contribute to increased IFNgamma production and the development of inflammatory disease in SOCS-1(-/-) mice. Here, we assess responses of SOCS-1-deficient cells to IL-12. Both IL-12-induced T cell proliferation and NK cytotoxic activity are enhanced in SOCS-1-deficient cells, relative to controls. To examine the contribution of continued IL-12 signaling to the SOCS-1(-/-) disease, we generated mice lacking both SOCS-1 and signal transducer and activator of transcription 4 (STAT4), an essential component of the IL-12 signaling pathway. SOCS-1(-/-) STAT4(-/-)mice have improved survival relative to SOCS-1(-/-) mice, but die between 1 and 2 months of age. We conclude that, in addition to IFNgamma, SOCS-1 regulates responses to IL-12.
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- CELL STIMULATORY FACTOR; INTERFERON-GAMMA-PRODUCTION; MOUSE IL-12 RECEPTOR; NATURAL-KILLER; T-CELLS; IMMUNE-RESPONSES; IFN-GAMMA; NK CELLS; IN-VIVO; TYROSINE PHOSPHORYLATION
- Publisher's Version
- https://doi.org/10.1074/jbc.M208586200
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2002-11-15 12:00:00