The Center for Biomedical Research, NHC Key Laboratory of Respiratory Diseases, Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
Front Immunol. 2021 May 4;12:663295. doi: 10.3389/fimmu.2021.663295. eCollection 2021.
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.
脓毒症是指感染引起的全身炎症反应综合征。它是全球重症监护病房患者的主要临床问题和死亡原因。脂肪量和肥胖相关蛋白 (FTO) 是主要的 -甲基腺苷脱甲基酶。然而，FTO 在炎症性疾病发病机制中的作用尚不清楚。我们在此表明，纳米颗粒介导的 -siRNA 递送至或 FTO 抑制剂恩他卡朋给药可显著抑制巨噬细胞活化，减轻脂多糖诱导的内毒素休克小鼠模型中的组织损伤并提高存活率。重要的是，巨噬细胞中 FTO 的缺失可通过 FoxO1/NF-κB 信号抑制 NLRP3 炎性体。总之，FTO 参与 LPS 诱导的脓毒性休克的炎症反应，抑制 FTO 有希望用于治疗脓毒性休克。
