代谢物
烷基化
刺
干扰素基因刺激剂
衍生工具(金融)
炎症
化学
免疫系统
败血症
半胱氨酸
新陈代谢
干扰素
基因
生物化学
先天免疫系统
酶
生物
催化作用
免疫学
金融经济学
经济
工程类
航空航天工程
作者
Weizhen Li,Yangguang Li,Jiaqi Kang,Haiyang Jiang,Wenjing Gong,Lijuan Chen,Cunxia Wu,Mingda Liu,Xiuwen Wu,Yun Zhao,Jianan Ren
出处
期刊:Cell Reports
[Elsevier]
日期:2023-03-01
卷期号:42 (3): 112145-112145
被引量:22
标识
DOI:10.1016/j.celrep.2023.112145
摘要
The Krebs cycle-derived metabolite itaconate, whose production is catalyzed by immune response gene 1 (IRG1), has potential to link immunity and metabolism in activated macrophages through alkylation or competitive inhibition of target proteins. In support of this, our previous study demonstrated that the stimulator of interferon genes (STING) signaling platform functions as a hub in macrophage immunity and has a profound impact on the prognosis of sepsis. Interestingly, we find that itaconate, an endogenous immunomodulator, can significantly inhibit the activation of STING signaling. Moreover, 4-octyl itaconate (4-OI), which is a permeable itaconate derivative, can alkylate cysteine sites 65, 71, 88, and 147 of STING, thereby inhibiting its phosphorylation. Furthermore, itaconate and 4-OI inhibit the production of inflammatory factors in sepsis models. Our results broaden the knowledge on the role of the IRG1-itaconate axis in immunomodulation and highlight itaconate and its derivatives as potential therapeutic agents in sepsis.
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