Granulocyte macrophage colony-stimulating factor and interleukin-5 activate STAT5 and induce CIS1 mRNA in human peripheral blood eosinophils
Granulocyte macrophage colony-stimulating factor and interleukin-5 activate STAT5 and induce CIS1 mRNA in human peripheral blood eosinophils
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DOI：
10.1165/ajrcmb.24.3.4238
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发表时间：
2001-03-01
影响因子：
6.4
通讯作者：
Malter, JS
中科院分区：
文献类型：
--
作者：
Bhattacharya, S;Stout, BA;Malter, JS
在这些研究中，我们检测了经粒细胞巨噬细胞集落刺激因子（GM-CSF）或白细胞介素（IL）-5处理的人外周血嗜酸性粒细胞中通过转录因子STAT 5的信号传导。酪氨酸磷酸化的STAT 5与胞质和核细胞组分相关。与活化一致，STAT 5依赖性基因、细胞因子诱导的含SH 2蛋白（CIS 1）的转录在细胞因子刺激后增强。这是首次报道IL-5在任何细胞类型中调节CIS 1基因表达。鉴于其在细胞因子信号传导中的作用，CIS 1上调可能有助于减弱IL-5和GM-CSF对嗜酸性粒细胞功能的调节。这些数据表明，在刺激的人外周血嗜酸性粒细胞中，活性核STAT 5参与调节IL-5和GM-CSF诱导基因。
In these studies, we examined signaling through the transcription factor STAT5 in human peripheral blood eosinophils after treatment with granulocyte macrophage colony-stimulating factor (GM-CSF) or interleukin (IL)-5, In response to either cytokine, STAT5 was rapidly tyrosine phosphorylated and acquired interferon gamma activation site (GAS) DNA binding activity. Tyrosine-phosphorylated STAT5 was associated with both cytosolic and nuclear cell fractions. Consistent with activation, the transcription of a STAT5-dependent gene, cytokine inducible, SH2-containing protein (CIS1), was enhanced after cytokine stimulation. This is the first report of IL-S regulation of CIS1 gene expression in any cell type. Given its role in cytokine signaling, CIS1 upregulation may serve to attenuate IL-5 and GM-CSF modulation of eosinophil function. These data suggest that active nuclear STAT5 participates in the regulation of IL-5 and GM-CSF-inducible genes in stimulated human peripheral blood eosinophils.