Signals transducers and activators of transcription (STAT)-induced STAT inhibitor-1 (SSI-1)/suppressor of cytokine signaling-1 (SOCS-1) suppresses tumor necrosis factor α-induced cell death in fibroblasts
Signals transducers and activators of transcription (STAT)-induced STAT inhibitor-1 (SSI-1)/suppressor of cytokine signaling-1 (SOCS-1) suppresses tumor necrosis factor α-induced cell death in fibroblasts
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DOI：
10.1073/pnas.090084797
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发表时间：
2000-05-09
影响因子：
11.1
通讯作者：
Kishimoto, T
中科院分区：
文献类型：
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作者：
Morita, Y;Naka, T;Kishimoto, T
信号转导子和转录激活子 (STAT) 诱导的 STAT 抑制剂-1 [SSI-1；也称为细胞因子信号传导抑制因子-1 (SOCS-1)]被确定为 Janus 激酶-STAT 信号传导的负反馈调节因子。我们之前生成了缺乏 SSI-1 基因 (SSI-1 -/-) 的小鼠，并发现 SSI-1 -/- 小鼠的胸腺细胞和脾细胞经历了加速凋亡。在本文中，我们发现缺乏 SSI-1 基因的小鼠胚胎成纤维细胞比同窝对照小鼠对肿瘤坏死因子-α (TNF-α) 诱导的细胞死亡更敏感。此外，被迫表达SSI-1(L929/SSI-1)但不表达SSI-3或SOCS-5的L929细胞对TNF-α诱导的细胞死亡具有抵抗力。此外，用 TNF-α 处理的 L929/SSI-1 细胞维持 p38 丝裂原激活蛋白 (MAP) 激酶的激活。相反，用TNF-α处理的SSI-1 -/- 鼠胚胎成纤维细胞几乎没有显示出任何p38 MAP激酶的激活。这些发现表明，SSI-1 抑制 TNF-α 诱导的细胞死亡，这是由 p38 MAP 激酶信号传导介导的。
Signal transducers and activators of transcription (STAT)-induced STAT inhibitor-1 [SSI-1; also known as suppressor of cytokine signaling-1 (SOCS-1)] was identified as a negative feedback regulator of Janus kinase-STAT signaling. We previously generated mice lacking the SSI-1 gene (SSI-1 -/-) and showed that thymocytes and splenocytes in SSI-1 -/- mice underwent accelerated apoptosis. In this paper, we show that murine embryonic fibroblasts lacking the SSI-1 gene are more sensitive than their littermate controls to tumor necrosis factor-alpha (TNF-alpha)-induced cell death. In addition, L929 cells forced to express SSI-l (L929/SSI-1), but not SSI-3 or SOCS-5, are resistant to TNF-alpha-induced cell death. Furthermore L929/SSI-1 cells treated with TNF-alpha sustain the activation of p38 mitogen-activated protein (MAP) kinase. In contrast, SSI-1 -/- murine embryonic fibroblasts treated with TNF-alpha show hardly any activation of p38 MAP kinase. These findings suggest that SSI-1 suppresses TNF-alpha-induced cell death, which is mediated by p38 MAP kinase signaling.