STAT3 exerts two-way regulation in the biological effects of IL-6 in M1 leukemia cells
STAT3 exerts two-way regulation in the biological effects of IL-6 in M1 leukemia cells
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DOI：
10.1016/s0145-2126(00)00157-0
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发表时间：
2001-06-01
影响因子：
2.7
通讯作者：
Sun, YX
中科院分区：
文献类型：
--
作者：
Zhang, JY;Shen, BF;Sun, YX
信号转导子和转录激活子（STAT）蛋白质已经牵涉到精氨酸调节的增殖、分化和细胞存活。白细胞介素-6（IL-6）。一种多效性细胞因子，诱导M1急性髓性白血病细胞中STAT 3的稳健和持续活化。其继而响应于IL-6而经历生长停滞、终末分化和凋亡。STAT 3激活在IL-6介导的M1细胞应答中的作用尚未完全了解。我们将STAT 3反义cDNA导入M1细胞。STAT 3反义cDNA可阻断STAT 3的表达及IL-6诱导的STAT 3酪氨酸磷酸化和DNA结合。并导致M1转化体中IL-6诱导的G（0）/G（1）期生长停滞和巨噬细胞分化的减少。这一观察结果与以前的报道一致，并证实了STAT 3在IL-6诱导的MI白血病细胞生长停滞和终末分化中起重要作用。另一方面，STAT 3反义cDNA增强了IL-6诱导的MI细胞凋亡，细胞周期分析证实了这一点。DNA片段化分析和Caspase 3的p17活性片段的检测。因为增殖抑制和分化诱导代表负信号，而存活维持代表正信号。结论STAT 3对IL-6在M1白血病细胞中的生物学效应具有双向调节作用。(C)2001爱思唯尔科技有限公司版权所有。
The signal transducer and activator of transcription (STAT) proteins have been implicated in cytokine-regulated proliferation, differentiation and cell survival. Interleukin-6 (IL-6). a pleiotropic cytokine, induces a robust and sustained activation of STAT3 in M1 acute myeloid leukemia cells. which in turn undergo growth arrest, terminal differentiation and apoptosis in response to IL-6. The roles of STAT3 activation in IL-6-mediated responses in M1 cells are not fully understood. We introduced STAT3 antisense cDNA into M1 cells. STAT3 antisense cDNA blocked the expression and IL-6-induced tyrosine phosphorylation and DNA binding of STAT3. and resulted in reduction of both IL-6-induced growth arrest at G(0)/G(1) phase and macrophage differentiation in the M1 transformants. This observation is in accordance with previous reports and confirms that STAT3 plays an essential role in IL-6-induced growth arrest and terminal differentiation in MI leukemia cells. On the other hand, STAT3 antisense cDNA auizmented IL-6-induced apoptosis of MI cells, which was supported by the cell cycle assay. DNA fragmentation assay and detection of the p17 active fragment of Caspase 3. As proliferation inhibition and differentiation induction stands for a negative signal, while survival maintenance stands for a positive signal. we conclude that STAT3 exerts two-way regulation on the biological effects of IL-6 in M1 leukemia cells. (C) 2001 Elsevier Science Ltd. All rights reserved.