AUTHOR=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 

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.663295

DOI=10.3389/fimmu.2021.663295

ISSN=1664-3224

ABSTRACT=<p>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 <italic>N</italic><sup>6</sup>-methyladenosine demethylase. However, the role of FTO in the pathogenesis of inflammatory diseases remains unclear. We herein show that nanoparticle-mediated <italic>Fto</italic>-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.</p>