Metabolomics

Dataset Information

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4-Octyl itaconate as a metabolite derivative inhibits inflammation via alkylation of STING


ABSTRACT:

The Krebs cycle-derived metabolite itaconate, whose production is catalyzed by immune response gene 1 (IRG1), has excellent 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 found 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, could alkylate cysteine sites 65, 71, 88, and 147 of STING, thereby inhibiting its phosphorylation and downregulating the production of related inflammatory factors. Furthermore, itaconate and 4-OI inhibited the production of inflammatory factors in sepsis models. Our results have broadened the role of the IRG1-Itaconate axis in immunomodulation and highlighted itaconate and its derivatives as potential therapeutic agents in sepsis.

INSTRUMENT(S): Liquid Chromatography MS - negative - hilic

PROVIDER: MTBLS5877 | MetaboLights | 2023-01-15

REPOSITORIES: MetaboLights

Dataset's files

Source:
Action DRS
BLANK_NEG.wiff Wiff
D16h1_NEG.wiff Wiff
D16h2_NEG.wiff Wiff
D16h3_NEG.wiff Wiff
D6h1_NEG.wiff Wiff
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Publications

4-octyl itaconate as a metabolite derivative inhibits inflammation via alkylation of STING.

Li Weizhen W   Li Yangguang Y   Kang Jiaqi J   Jiang Haiyang H   Gong Wenbin W   Chen Lijuan L   Wu Cunxia C   Liu Mingda M   Wu Xiuwen X   Zhao Yun Y   Ren Jianan J  

Cell reports 20230228 3


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,  ...[more]

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