Sensitization of IFN-γ Jak-STAT signaling during macrophage activation
Sensitization of IFN-γ Jak-STAT signaling during macrophage activation
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DOI：
10.1038/ni828
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发表时间：
2002-09-01
影响因子：
30.5
通讯作者：
Ivashkiv, LB
中科院分区：
文献类型：
--
作者：
Hu, XY;Herrero, C;Ivashkiv, LB
信号转导的一个普遍范例是配体诱导的反馈抑制和信号的脱敏。我们发现，未激活巨噬细胞的亚阈值浓度的干扰素 -γ（IFN -γ）增加了它们对后续IFN -γ刺激的敏感性；这导致信号转导和转录激活因子1（STAT1）的激活增加以及IFN -γ依赖性基因激活增加。IFN -γ信号转导的致敏是由低剂量的IFN -γ诱导STAT1表达所介导的，低剂量的IFN -γ不会有效诱导反馈抑制。在体内注射IFN -γ后，IFN -γ信号转导被致敏，并且在注射脂多糖后以及在类风湿性关节炎滑膜细胞中，STAT1表达增加。这些结果确定了一种使巨噬细胞对低浓度的IFN -γ致敏并调节急性和慢性炎症中IFN -γ反应的机制。
A general paradigm in signal transduction is ligand-induced feedback inhibition and the desensitization of signaling. We found that subthreshold concentrations of interferon-gamma (IFN-gamma), which did not activate macrophages, increased their sensitivity to subsequent IFN-gamma stimulation; this resulted in increased signal transducer and activator of transcription 1 (STAT1) activation and increased IFN-gamma-dependent gene activation. Sensitization of IFN-gamma signaling was mediated by the induction of STAT1 expression by low doses of IFN-gamma that did not effectively induce feedback inhibition. IFN-gamma signaling was sensitized in vivo after IFN-gamma injection, and STAT1 expression was increased after injection of lipopolysaccharide and in rheumatoid arthritis synovial cells. These results identify a mechanism that sensitizes macrophages to low concentrations of IFN-gamma and regulates IFN-gamma responses in acute and chronic inflammation.