STAT5a induces endotoxin tolerance by alleviating pyroptosis in kupffer cells
STAT5a induces endotoxin tolerance by alleviating pyroptosis in kupffer cells
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STAT5a 通过减轻库普弗细胞焦亡来诱导内毒素耐受
DOI：
10.1016/j.molimm.2020.03.016
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发表时间：
2020-06-01
影响因子：
3.6
通讯作者：
Gong, Jianping
中科院分区：
文献类型：
--
作者：
Wang, Tao;Zhong, Hua;Gong, Jianping
焦亡是一种新发现的程序性细胞死亡类型，会影响巨噬细胞的内毒素耐受性。然而，需要发现作用于 nod 样受体 3 (Nlrp3) 炎性体和 caspase1 激活以阻止焦亡并导致脓毒症耐受和存活的因素。在这里，我们发现信号转导子和转录激活子 5A (STAT5a) 抑制 Kupffer 细胞 (KC) 的焦亡并在脓毒症模型中诱导内毒素耐受 (ET)。 STAT5a 的慢病毒敲低导致 KC 焦亡增强，通过复杂的 NF-κ b 信号调节增加 IL-1 β 的产生并减少 IL-10 的产生。因此，我们的研究结果揭示了 STAT5a 介导的 KC 内毒素耐受的新机制。
Pyroptosis, a newly discovered type of programmed cell death, affects endotoxin tolerance in macrophages. However, the factors acting on the nod-like receptor 3 (Nlrp3) inflammasome and caspase1 activation to impede pyroptosis and resulting in tolerance and survival in sepsis were needed to discovered. Here, we found that signal transducer and activator of transcription 5A (STAT5a) restrains pyroptosis in Kupffer cells (KCs) and induces endotoxin tolerance (ET) in a sepsis model. The lentiviral knockdown of STAT5a led to enhanced pyroptosis in KCs, increased IL-1 beta production and decreased IL-10 production via intricate NF-kappa b signaling regulation. Thus, our findings reveal a novel mechanism of STAT5a-midiated endotoxin tolerance in KCs.