Aerobic Exercise Attenuates Acute Lung Injury Through NET Inhibition

Abstract

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.

Role of increasing the aerobic capacity on improving the function of immune and respiratory systems in patients with coronavirus (COVID-19): A review

“…Also, increasing the aerobic capacity can produce a preventive and curable role against respiratory infections and disorders. It can prevent or treat both pneumonia [28e30] and acute respiratory distress syndrome (ARDS) [11,31,32], which are the common disorders develop with COVID-19 and lead to a respiratory system failure. The effect of increasing the aerobic capacity on improving lung functions and preventing lung damage can be summarized into four mechanisms.…”

“…Vieira et al [91] have reported that increasing the aerobic capacity increases levels of IL-10, which is an essential element in immunity against acute lung inflammations and injuries. A very recent study conducted by Shi et al [32] has shown that 5-weeks of mild aerobic exercises can prevent acute lung injury in mice by producing neutrophil extracellular traps (NETs) inhibition, which plays a vital role in acute lung injury. NETs are secreted by stimulated neutrophils and consist mainly of histones, DNA, myeloperoxidase, and neutrophil elastase (NE).…”

Short-Term Effects of a Conditioning Telerehabilitation Program in Confined Patients Affected by COVID-19 in the Acute Phase. A Pilot Randomized Controlled Trial

“…In that sense, it has been argued that continuing physical activity during confinement to stay healthy and maintain immune system function is a reasonable health rationale [ 7 ], as confinement generates serious problems in the physical and nutritional state of patients [ 8 ]. Indeed, exercise can play an essential role against respiratory infections and disorders, such as pneumonia and acute respiratory distress syndrome (ARDS), which are two common disorders with COVID-19 [ 9 , 10 ] and, in people in the lockdown period, it is strongly recommended to decrease the risk factors of COVID-19, improving immune and respiratory systems’ function to allow better body response against the disease [ 11 ].…”

Kupffer cell activation by different microbial lysates: Toll‐like receptor‐2 plays pivotal role on thromboxane A2 production in mice and humans

“…In addition to THP‐1 cells, the NF‐κB and MAPK phosphorylation levels in LPS‐stimulated peritoneal macrophages and RAW 264.7 macrophages infected with S. aureus also increased [20,21]. Alveolar macrophages isolated from LPS‐treated mice also showed a higher ratio of phosphorus‐NF‐kB/ NF‐kB that confirmed the relation between TLR‐2/4 and MAPK/ NF‐kB phosphorylation [22]. Previous studies have shown that TLR activation can regulate COX‐1 and COX‐2 through the MyD88‐dependent NF‐κB pathway, and cause changes in vasoactive factors such as Prostaglandin (PG) [23].…”