IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages
IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages
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DOI：
10.1038/ni938
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发表时间：
2003-06-01
影响因子：
30.5
通讯作者：
Yoshimura, A
中科院分区：
文献类型：
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作者：
Yasukawa, H;Ohishi, M;Yoshimura, A
白细胞介素6 （IL-6）是一种促炎细胞因子，而IL-10是一种抗炎细胞因子。尽管信号换能器和转录激活因子3 （STAT3）对于IL-6和IL-10的功能都是必不可少的，但这两种细胞因子如何具有如此相反的功能尚不清楚。本研究表明，细胞因子信号传导抑制因子3 （SOCS3）是这两种细胞因子分化作用的关键调节因子。在缺乏Socs3基因或携带gp130中Socs3结合位点突变的巨噬细胞中，脂多糖诱导的肿瘤坏死因子（TNF）和IL-12的产生被IL-10和IL-6抑制。SOCS3特异性地阻止STAT3被IL-6激活，而不是IL-10。综上所述，这些数据表明SOCS3选择性地阻断IL-6的信号传导，从而阻止其抑制LPS信号传导的能力。
Whereas interleukin-6 (IL-6) is a proinflammatory cytokine, IL-10 is an anti-inflammatory cytokine. Although signal transducer and activator of transcription 3 (STAT3) is essential for the function of both IL-6 and IL-10, it is unclear how these two cytokines have such opposing functions. Here we show that suppressor of cytokine signaling 3 (SOCS3) is a key regulator of the divergent action of these two cytokines. In macrophages lacking the Socs3 gene or carrying a mutation of the SOCS3-binding site in gp130, the lipopolysaccharide-induced production of tumor necrosis factor (TNF) and IL-12 is suppressed by both IL-10 and IL-6. SOCS3 specifically prevents activation of STAT3 by IL-6 but not IL-10. Taken together, these data indicate that SOCS3 selectively blocks signaling by IL-6, thereby preventing its ability to inhibit LPS signaling.