Aerobic Exercise Attenuates Acute Lung Injury Through NET Inhibition

Frontiers in Immunology

Luyu Yang¹  Hui Shi²  Tingting Liu²  David C. Nieman³  Peijie Chen⁴  Yanqiu Cui⁴  Yue Shi⁴  Fei Li⁵ 

[1] Department of General Surgery, Cancer Metastasis Institute, Huashan Hospital, Fudan University, Shanghai, China;Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;North Carolina Research Campus, Appalachian State University, Kannapolis, NC, United States;School of Kinesiology, Shanghai University of Sport, Shanghai, China;School of Physical Education and Sport Training, Shanghai University of Sport, Shanghai, China;

关键词: acute lung injury;    aerobic exercise;    neutrophil extracellular traps;    alveolar macrophages;    inflammation;   

DOI  :  10.3389/fimmu.2020.00409

来源: DOAJ

【 摘 要 】

Introduction: Aerobic exercise improves lung inflammation in acute lung injury (ALI), but its mechanism remains unknown. Neutrophil extracellular traps (NETs) play an important role in LPS-induced ALI, and a positive correlation exists between NET formation and proinflammatory macrophage polarization. This study investigated whether aerobic exercise reduces the pro-inflammatory polarization of alveolar macrophages (AMs) by inhibiting the excessive release of NETs and then alleviating the inflammatory response of ALI.Methods: C57BL/6 male mice were randomly divided into four groups: sedentary group (CON), sedentary and extra-pulmonary LPS injection group (LPS), 5-weeks aerobic training intervention and LPS injection group (EXE+LPS), and DNase I plus LPS injection group (DNase+LPS). Twenty-four hours after drug injection, bronchoalveolar lavage fluid (BALF), AM, and lung tissues were obtained to detect inflammatory responses, NET formation, macrophage polarization, and protein activation. In the in vitro study, a murine AM cell line, designated MH-S, was stimulated with LPS, purified NETs, and NETs plus DNase I.Results: EXE+LPS and DNase+LPS mice exhibited reduced neutrophil infiltration, decreased NET release, and lower pro-inflammatory polarization of AM compared with LPS mice. Subsequently, Western blot showed inhibition of the phosphorylation of MAPK and NF-κB proteins of AMs in EXE+LPS and DNase+LPS mice compared with LPS mice. Lastly, stimulation of MH-S cells by NETs revealed a trend for pro-inflammatory cell polarization, with NF-κB protein activation at 8 h and ERK1/2 activation at 1, 2, and 8 h.Conclusions: Aerobic exercise alleviated ALI through NET-induced AM pro-inflammatory polarization involving ERK1/2 and NF-κB signaling.

【 授权许可】

Unknown