Suppressor of Cytokine Signaling-1 Attenuates the Duration of Interferon γ Signal Transduction in Vitro and in Vivo

Abstract

Suppressor of cytokine signaling-1 (SOCS-1) is a cytokine-inducible intracellular protein that functions to negatively regulate cytokine signal transduction pathways. Studies in vitro have shown that constitutive overexpression of SOCS-1 inhibits signaling in response to a range of cytokines, including interferons (IFN). Mice lacking SOCS-1 die from a complex disease characterized by liver degeneration and massive inflammation. Whereas there is clear evidence of increased IFNγ signaling in SOCS-/- mice, it is unclear to what extent this is due to increased IFNγ levels or to increased IFNγ sensitivity. Here we have used SOCS-1-/- IFNγ-/- mice, which remain healthy and produce no endogenous IF..