Targeted Inhibition of FTO Demethylase Protects Mice Against LPS-Induced Septic Shock by Suppressing NLRP3 Inflammasome

Sepsis refers to the systemic inflammatory response syndrome caused by infection. It is a major clinical problem and cause of death for patients in intensive care units worldwide. The Fat mass and obesity-related protein (FTO) is the primary -methyladenosine demethylase. However, the role of FTO in...

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Bibliographic Details
Published in:Frontiers in immunology 2021-05, Vol.12, p.663295-663295
Main Authors: Luo, Jiahui, Wang, Faxi, Sun, Fei, Yue, Tiantian, Zhou, Qing, Yang, Chunliang, Rong, Shanjie, Yang, Ping, Xiong, Fei, Yu, Qilin, Zhang, Shu, Wang, Cong-Yi, Li, Jinxiu
Format: Article
Language:English
Subjects:
entacapone
FTO
Immunology
inflammasome
N6-methyladenosine
sepsis
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Summary:Sepsis refers to the systemic inflammatory response syndrome caused by infection. It is a major clinical problem and cause of death for patients in intensive care units worldwide. The Fat mass and obesity-related protein (FTO) is the primary -methyladenosine demethylase. However, the role of FTO in the pathogenesis of inflammatory diseases remains unclear. We herein show that nanoparticle-mediated -siRNA delivery or FTO inhibitor entacapone administration dramatically inhibited macrophage activation, reduced the tissue damage and improved survival in a mouse model of LPS-induced endotoxic shock. Importantly, ablation of FTO could inhibit NLRP3 inflammasome through FoxO1/NF-κB signaling in macrophages. In conclusion, FTO is involved in inflammatory response of LPS-induced septic shock and inhibition of FTO is promising for the treatment of septic shock.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.663295