Here we show that overexpression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3 in liver causes insulin resistance and an increase in the key regulator of fatty acid synthesis in liver, sterol regulatory element-binding protein (SREBP)-1c.
Compared to STAT3+/+ mice, both SOCS3 protein expression was markedly lower in the STAT3−/− mice (Figure (Figure7).7). Thus, the loss of STAT3 expression may enhance lung inflammation by diminishing the anti-inflammatory responses mediated by SOCS3.
SOCS3(-/-) DCs expressed lower levels of class II MHC, CD40, CD86, and IL-12 than wild-type (WT)-DCs both in vitro and in vivo, and showed constitutive activation of STAT3.
ompared to STAT3+/+ mice, both SOCS3 protein expression was markedly lower in the STAT3−/− mice (Figure (Figure7).7). Thus, the loss of STAT3 expression may enhance lung inflammation by diminishing the anti-inflammatory responses mediated by SOCS3.
We demonstrated that SOCS3 deletion in the liver resulted in hyperactivation of STAT3 and promoted ConA- and chemical-induced liver fibrosis.
By contrast, Socs3 was found to be a major regulator of IL-23-mediated Stat3 phosphorylation and Th17 generation, and Stat3 directly binds to the IL-17A and IL-17F promoters. We conclude that Socs3 is an essential negative regulator of IL-23 signaling, inhibition of which constrains the generation of Th17 differentiation.
Restoration of SOCS-3 in lung cancer cells where SOCS-3 was methylation-silenced resulted in the down-regulation of active STAT3, induction of apoptosis, and growth suppression.
(from text) Here we show that phosphorylation of STAT3 is prolonged in mouse Socs3-deficient macrophages after stimulation with interleukin-6 (IL-6) but not IL-10, indicating that SOCS3 specifically affects signaling mediated by IL-6 and gp130.
We further show that activation of STAT3 was inhibited by SOCS3 overexpression as well as by anti-IL-6 treatment during IgG IC-induced lung injury, as determined by EMSA.
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