PMC:1064873 / 1693-3413 JSONTXT

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Upon phosphorylation, STAT1 and STAT3 proteins form homodimers or heterodimers, rapidly translocate into the nucleus, and modulate gene transcription. Intriguingly, STAT3 is indispensable for both IL-10-derived anti-inflammatory and IL-6-derived proinflammatory responses [4]. Studies of cell-type-specific STAT3-deficient mice have shown that STAT3 activation is essential for IL-10-mediated anti-inflammatory reactions in macrophages and neutrophils [5], but is responsible for IL-6-mediated prevention of apoptosis in T cells [6]. The suppressor of cytokine signaling (SOCS) proteins have been identified as a family of endogenous JAK kinase inhibitors that can act in classic feedback inhibition loops, but their roles as the mediators of crosstalk inhibition by opposing cytokine signaling pathways have been clarified [7]. Recent studies indicate that SOCS3 plays a key role in regulating the divergent action of IL-10 and IL-6, by specifically blocking STAT3 activation induced by IL-6 but not that induced by IL-10 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