Frontiers in Immunology (May 2021)

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

  • Jiahui Luo,
  • Faxi Wang,
  • Fei Sun,
  • Tiantian Yue,
  • Qing Zhou,
  • Chunliang Yang,
  • Shanjie Rong,
  • Ping Yang,
  • Fei Xiong,
  • Qilin Yu,
  • Shu Zhang,
  • Cong-Yi Wang,
  • Jinxiu Li

DOI
https://doi.org/10.3389/fimmu.2021.663295
Journal volume & issue
Vol. 12

Abstract

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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 N6-methyladenosine demethylase. However, the role of FTO in the pathogenesis of inflammatory diseases remains unclear. We herein show that nanoparticle-mediated Fto-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.

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