Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6-induced survival signals in T cells
Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6-induced survival signals in T cells
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DOI：
10.1128/mcb.21.19.6615-6625.2001
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发表时间：
2001-10-01
影响因子：
5.3
通讯作者：
Hirano, T
中科院分区：
文献类型：
--
作者：
Narimatsu, M;Maeda, H;Hirano, T
信号转导因子和转录激活因子3 （STAT3）介导多种生长因子和细胞因子的信号，包括白细胞介素-6 （IL-6）。在某些IL-6应答细胞系中，stat3基因通过其启动子中的复合IL-6应答元件（包含stat3结合元件（SBE）和环状amp应答元件）被stat3自动调节。为了揭示体内stat3自动调节的性质和作用，我们产生了SBE突变的小鼠（stat3(mSBe)）。完整的SBE对于il -6诱导的脾脏stat3基因激活至关重要，尤其是在红髓区、肾脏以及成熟和未成熟的T淋巴细胞中。然而，对于il -6诱导的肝细胞stat3基因激活，SBE不是必需的。尽管存在IL-6，但stat3（mSBE/mSBE）小鼠的T淋巴细胞比野生型小鼠的T淋巴细胞更容易凋亡。与此一致的是，STAT3的直接靶基因Pim-1和junB基因的il -6依赖性激活在STAT3 （mSBE/mSBE）小鼠的T淋巴细胞中减弱。因此，stat3基因的组织特异性自动调节在体内起作用，并在il -6诱导的T细胞抗凋亡信号传导中发挥作用。
Signal transducer and activator of transcription 3 (STAT3) mediates signals of various growth factors and cytokines, including interleukin-6 (IL-6). In certain IL-6-responsive cell lines, the stat3 gene is autoregulated by STAT3 through a composite IL-6 response element in its promoter that contains a STAT3-binding element (SBE) and a cyclic AMP-responsive element. To reveal the nature and roles of the stat3 autoregulation in vivo, we generated mice that harbor a mutation in the SBE (stat3(mSBe)). The intact SBE was crucial for IL-6-induced stat3 gene activation in the spleen, especially in the red pulp region, the kidney, and both mature and immature T lymphocytes. The SBE was not required, however, for IL-6-induced stat3 gene activation in hepatocytes. T lymphocytes from the stat3(mSBE/mSBE) mice were more susceptible to apoptosis despite the presence of IL-6 than those from wild-type mice. Consistent with this, IL-6-dependent activation of the Pim-1 and junB genes, direct target genes for STAT3, was attenuated in T lymphocytes of the stat3(mSBE/mSBE) mice. Thus, the tissue-specific autoregulation of the stat3 gene operates in vivo and plays a role in IL-6-induced antiapoptotic signaling in T cells.