Specific ablation of Stat3β distorts the pattern of Stat3-responsive gene expression and impairs recovery from endotoxic shock
Specific ablation of Stat3β distorts the pattern of Stat3-responsive gene expression and impairs recovery from endotoxic shock
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DOI：
10.1016/s0092-8674(02)00636-0
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发表时间：
2002-02-08
期刊：
影响因子：
64.5
通讯作者：
Desiderio, S
中科院分区：
文献类型：
--
作者：
Yoo, JY;Huso, DL;Desiderio, S
Stat 3是一种由IL-6家族细胞因子激活的转录因子，其基因的选择性剪接产生两种亚型：Stat 3 α和显性阴性变体Stat 3 β。通过基因靶向产生Stat 3 β缺陷小鼠。尽管完整的表达和磷酸化的Stat 3 α，整体Stat 3活性受损的Stat 3 β（-/-）细胞。Stat 3 β（+/+）和Stat 3 β（-/-）细胞中转录的总体比较显示稳定的差异。Stat 3 β缺陷小鼠表现出内毒素休克恢复减少和肝脏内毒素诱导基因亚组的高反应性。野生型小鼠对内毒素的肝脏反应伴随着Stat 3 β与Stat 3 α比值的一过性增加。这些发现表明Stat 3 β在控制全身炎症中的关键作用。
Alternative splicing of the gene for Stat3, a transcription factor activated by the IL-6 family of cytokines, produces two isoforms: Stat3alpha and a dominant-negative variant, Stat3beta. Stat3beta-deficient mice were generated by gene targeting. Despite intact expression and phosphorylation of Stat3alpha, overall Stat3 activity was impaired in Stat3beta(-/-) cells. Global comparison of transcription in Stat3beta(+/+) and Stat3beta(-/-) cells revealed stable differences. Stat3beta-deficient mice exhibit diminished recovery from endotoxic shock and hyper-responsiveness of a subset of endotoxin-inducible genes in liver. The hepatic response to endotoxin in wild-type mice is accompanied by a transient increase in the ratio of Stat3beta to Stat3alpha. These findings indicate a critical role for Stat3beta in the control of systemic inflammation.