在巨噬细胞中，白细胞介素-6在缺乏细胞因子信号转导抑制因子3（SOCS3）的情况下会诱导抗炎反应。

IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages.

作者信息

Yasukawa Hideo, Ohishi Masanobu, Mori Hiroyuki, Murakami Masaaki, Chinen Takatoshi, Aki Daisuke, Hanada Toshikatsu, Takeda Kiyoshi, Akira Shizuo, Hoshijima Masahiko, Hirano Toshio, Chien Kenneth R, Yoshimura Akihiko

机构信息

Institute of Molecular Medicine and Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0641, USA.

出版信息

Nat Immunol. 2003 Jun;4(6):551-6. doi: 10.1038/ni938. Epub 2003 May 18.

DOI:10.1038/ni938

PMID:12754507

Abstract

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.

摘要

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。尽管信号转导和转录激活因子3（STAT3）对IL-6和IL-10的功能都至关重要，但尚不清楚这两种细胞因子为何具有如此相反的功能。在此我们表明，细胞因子信号转导抑制因子3（SOCS3）是这两种细胞因子不同作用的关键调节因子。在缺乏Socs3基因或gp130中携带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的产生受到IL-10和IL-6两者的抑制。SOCS3特异性地阻止IL-6而非IL-10激活STAT3。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。