Negative Regulation of Interleukin-12 Signaling by Suppressor of Cytokine Signaling-1
Copyright policy )Negative Regulation of Interleukin-12 Signaling by Suppressor of Cytokine Signaling-1
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.
- Harvard University United States
- Melbourne Health Australia
- Royal Melbourne Hospital Australia
- Walter and Eliza Hall Institute of Medical Research Australia
Mice, Knockout, Mice, Inbred BALB C, Dose-Response Relationship, Drug, Receptors, Interleukin-12, Receptors, Interleukin, STAT4 Transcription Factor, Flow Cytometry, Interleukin-12, DNA-Binding Proteins, Killer Cells, Natural, Mice, Inbred C57BL, Repressor Proteins, Interferon-gamma, Mice, Gene Expression Regulation, Animals, Carrier Proteins, Cell Division, Cells, Cultured, Signal Transduction
Mice, Knockout, Mice, Inbred BALB C, Dose-Response Relationship, Drug, Receptors, Interleukin-12, Receptors, Interleukin, STAT4 Transcription Factor, Flow Cytometry, Interleukin-12, DNA-Binding Proteins, Killer Cells, Natural, Mice, Inbred C57BL, Repressor Proteins, Interferon-gamma, Mice, Gene Expression Regulation, Animals, Carrier Proteins, Cell Division, Cells, Cultured, Signal Transduction
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).96 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!