Aerobic Exercise Attenuates Acute Lung Injury Through NET Inhibition
Aerobic Exercise Attenuates Acute Lung Injury Through NET Inhibition
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DOI：
10.3389/fimmu.2020.00409
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发表时间：
2020-03-19
影响因子：
7.3
通讯作者：
Chen, Peijie
中科院分区：
文献类型：
--
作者：
Shi, Yue;Liu, Tingting;Chen, Peijie
前言：有氧运动可改善急性肺损伤（ALI）的肺部炎症，但其机制尚不清楚。神经元细胞外陷阱（NETs）在LPS诱导的ALI中起重要作用，并且NETs的形成与促炎性巨噬细胞极化呈正相关。本研究旨在探讨有氧运动是否通过抑制NET的过度释放而降低肺泡巨噬细胞（AM）的促炎性极化，进而减轻ALI的炎症反应。安静组（CON）、安静+肺外注射LPS组（LPS）、5周有氧训练干预+LPS注射组（EXE+LPS）、DNase Ⅰ + LPS注射组（DNase+LPS）。给药后24 h，取支气管肺泡灌洗液（BALF）、AM和肺组织，检测炎症反应、NET形成、巨噬细胞极化和蛋白活化。在体外研究中，小鼠AM细胞系，命名为MH-S，用LPS刺激，纯化的NET，和NET加DNase I.结果：EXE+LPS和DNase+LPS小鼠表现出减少中性粒细胞浸润，减少NET释放，和较低的AM促炎性极化与LPS小鼠相比。Western blot结果显示，与LPS小鼠相比，EXE+LPS和DNase+LPS小鼠AM的MAPK和NF-κ B B蛋白磷酸化水平明显降低。最后，NET刺激MH-S细胞揭示了促炎细胞极化的趋势，NF-κ B蛋白在8 h活化，ERK 1/2在1，2和8 h活化。结论：有氧运动通过NET诱导的AM促炎极化（涉及ERK 1/2和NF-κ B信号）减轻ALI。
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-kappa B 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-kappa B 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-kappa B signaling.