Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
Department of Surgery, Western Michigan University Homer Stryker, MD, School of Medicine, Kalamazoo, Michigan.
Acta Physiol (Oxf). 2019 Mar;225(3):e13194. doi: 10.1111/apha.13194. Epub 2018 Oct 22.
Stimulator of interferons genes (STING) is an adaptor protein that plays a critical role in the secretion of type I interferons and pro-inflammatory cytokines in response to cytosolic nucleic acid. Recent research indicates the involvement of the STING pathway in uncontrolled inflammation, sepsis, and shock. STING signaling is significantly up-regulated in human sepsis, and STING agonists are suggested to contribute to the pathogenesis of sepsis and shock. Nevertheless, little is known about the consequences of activated STING-mediated signaling during sepsis. It has been shown that aberrant activation of the STING-dependent way can result in increased inflammation, type I interferons responses, and cell death (including apoptosis, necroptosis, and pyroptosis). In addition, autophagy modulation has been demonstrated to protect against multiple organs injuries in animal sepsis model. However, impaired autophagy may contribute to the aberrant activation of STING signaling, leading to uncontrolled inflammation and cell death. Here we present a comprehensive review of recent advances in the understanding of STING signaling, focusing on the regulatory mechanisms and the roles of this pathway in sepsis.
干扰素基因刺激物 (STING) 是一种衔接蛋白，在细胞溶质核酸反应中，对于 I 型干扰素和促炎细胞因子的分泌起着关键作用。最近的研究表明，STING 通路参与了失控性炎症、败血症和休克。在人类败血症中，STING 信号显著上调，并且 STING 激动剂被认为有助于败血症和休克的发病机制。然而，对于败血症期间激活的 STING 介导的信号转导的后果知之甚少。已经表明，STING 依赖性途径的异常激活会导致炎症增加、I 型干扰素反应和细胞死亡（包括细胞凋亡、坏死性凋亡和细胞焦亡）。此外，已经证明自噬调节可防止动物败血症模型中多个器官损伤。然而，自噬功能障碍可能导致 STING 信号的异常激活，导致失控性炎症和细胞死亡。在这里，我们全面回顾了对 STING 信号转导的理解的最新进展，重点介绍了该途径在败血症中的调节机制和作用。
