Pivotal role of signal transducer and activator of transcription (Stat)4 and Stat6 in the innate immune response during sepsis.
Pivotal role of signal transducer and activator of transcription (Stat)4 and Stat6 in the innate immune response during sepsis.
复制标题
信号传感器和转录激活因子（Stat）4和STAT6在败血症期间先天免疫反应中的关键作用。
DOI：
10.1084/jem.193.6.679
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发表时间：
2001-03-19
影响因子：
15.3
通讯作者：
Kunkel, S L
中科院分区：
文献类型：
--
作者：
Matsukawa, A;Kaplan, M H;Hogaboam, C M;Lukacs, N W;Kunkel, S L
信号转导子和转录激活子（Stat）4和Stat 6是分别提供1型和2型反应的转录因子。在此，我们探讨了Stat 4和Stat 6在脓毒性腹膜炎先天免疫中的作用。与野生型（WT）小鼠相比，Stat 4 −/−和Stat 6 −/−小鼠对致死性具有抗性。在机制水平上，Stat 6 −/−小鼠的细菌水平远低于WT小鼠，这与白细胞介素（IL）-12，肿瘤坏死因子（TNF）-α，巨噬细胞衍生的趋化因子（MDC）和C10的腹膜水平增加有关，已知它们可以增强细菌清除。在Stat 4 −/−小鼠中，脓毒症期间的肝脏炎症和损伤显著改善，而不影响局部反应。该事件与肝脏IL-10和IL-13水平升高相关，同时巨噬细胞炎性蛋白（MIP）-2和KC水平降低。在Stat 4 −/−小鼠中，脓毒症诱导的肾损伤也被消除，伴随着MIP-2和KC的肾水平降低，而不改变IL-10和IL-13水平。因此，Stat 6 −/−和Stat 4 −/−小鼠似乎通过平衡细胞因子反应分别增强局部细菌清除和调节全身器官损伤来抵抗脓毒性腹膜炎。这些结果清楚地突出了局部1型和全身2型细胞因子应答在脓毒症期间保护性免疫中的重要作用，其可以由Stat蛋白调节。
Signal transducer and activator of transcription (Stat)4 and Stat6 are transcription factors that provide type 1 and type 2 response, respectively. Here, we explored the role of Stat4 and Stat6 in innate immunity during septic peritonitis. Stat4−/− and Stat6−/− mice were resistant to the lethality compared with wild-type (WT) mice. At the mechanistic level, bacterial levels in Stat6−/− mice were much lower than in WT mice, which was associated with increased peritoneal levels of interleukin (IL)-12, tumor necrosis factor (TNF)-α, macrophage-derived chemokine (MDC), and C10, known to enhance bacterial clearance. In Stat4−/− mice, hepatic inflammation and injury during sepsis were significantly ameliorated without affecting local responses. This event was associated with increased hepatic levels of IL-10 and IL-13, while decreasing those of macrophage inflammatory protein (MIP)-2 and KC. Sepsis-induced renal injury was also abrogated in Stat4−/− mice, which was accompanied by decreased renal levels of MIP-2 and KC without altering IL-10 and IL-13 levels. Thus, Stat6−/− and Stat4−/− mice appeared to be resistant to septic peritonitis by enhancing local bacterial clearance and modulating systemic organ damage, respectively, via balancing cytokine responses. These results clearly highlight an important role of local type 1 and systemic type 2 cytokine response in protective immunity during sepsis, which can be regulated by Stat proteins.