Zhai Dongsheng, Ye Zichen, Jiang Yinghao, Xu Chengming, Ruan Banjun, Yang Yuan, Lei Xiaoying, Xiang An, Lu Huanyu, Zhu Zheng, Yan Zhao, Wei Di, Li Qingyang, Wang Li, Lu Zifan
State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an 710032, PR China.
Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an710032, PR China.
Mol Immunol. 2017 Dec;92:151-160. doi: 10.1016/j.molimm.2017.10.017. Epub 2017 Nov 1.
Sepsis is a life-threatening disease characterized by uncontrolled inflammatory responses upon pathogen infections, especially for the antibiotic-resistant strains, such as Methicillin-resistant S. aureus (MRSA). Here we demonstrated that a Mitochondria-derived peptide (MOTS-c) could significantly improve the survival rate and decrease bacteria loads in MRSA-challenged mice, accompanied with declined levels of pro-inflammatory cytokines, such as TNF-α, IL-6 and IL-1β, but with increased level of anti-inflammatory cytokine IL-10. Moreover this peptide enhanced bactericidal capacity of macrophages. Meanwhile, MOTS-c inhibited the phosphorylation mitogen-activated protein kinases (MAPK), and enhanced the expression of aryl hydrocarbon receptor (AhR) and signal transducer and activator of transcriptional 3 (STAT3) in macrophages. Overall, MOTS-c plays a beneficial role in curbing the overwhelming inflammatory bursts in the fight against MRSA infection. It may serve as a potential therapeutic agent in sepsis treatment. Highlight.
脓毒症是一种危及生命的疾病，其特征是病原体感染后出现不受控制的炎症反应，尤其是对于耐抗生素菌株，如耐甲氧西林金黄色葡萄球菌（MRSA）。在此我们证明，一种线粒体衍生肽（MOTS-c）可显著提高受MRSA攻击小鼠的存活率并降低细菌载量，同时促炎细胞因子如TNF-α、IL-6和IL-1β的水平下降，但抗炎细胞因子IL-10的水平升高。此外，该肽增强了巨噬细胞的杀菌能力。同时，MOTS-c抑制丝裂原活化蛋白激酶（MAPK）的磷酸化，并增强巨噬细胞中芳烃受体（AhR）和转录信号转导子与激活子3（STAT3）的表达。总体而言，MOTS-c在对抗MRSA感染时抑制过度炎症爆发中发挥有益作用。它可能作为脓毒症治疗的潜在治疗剂。重点。
