炎症
促炎细胞因子
染色质
表观遗传学
脂多糖
重编程
活性氧
免疫学
生物
氧化应激
巨噬细胞
基因
细胞生物学
内分泌学
遗传学
体外
作者
Mayoorey Murugathasan,Ardavan Jafari,Amandeep Amandeep,Syed Adeel Hassan,Matthew Chihata,Ali A. Abdul‐Sater
出处
期刊:American Journal of Physiology-cell Physiology
[American Physiological Society]
日期:2023-08-01
卷期号:325 (2): C429-C442
被引量:10
标识
DOI:10.1152/ajpcell.00130.2023
摘要
Despite its importance in protecting the host from infections and injury, excessive inflammation may lead to serious human diseases including autoimmune disorders, cardiovascular diseases, diabetes, and cancer. Exercise is a known immunomodulator; however, whether exercise causes long-term changes in inflammatory responses and how these changes occur are lacking. Here, we show that chronic moderate-intensity training of mice leads to persistent metabolic rewiring and changes to chromatin accessibility in bone marrow-derived macrophages (BMDMs), which, in turn, tempers their inflammatory responses. We show that BMDMs from exercised mice exhibited a decrease in lipopolysaccharide (LPS)-induced NF-κB activation and proinflammatory gene expression along with an increase in M2-like-associated genes when compared with BMDMs from sedentary mice. This was associated with improved mitochondrial quality and increased reliance on oxidative phosphorylation accompanied with reduced mitochondrial reactive oxygen species (ROS) production. Mechanistically, assay for transposase-accessible chromatin (ATAC)-seq analysis showed changes in chromatin accessibility of genes associated with inflammatory and metabolic pathways. Overall, our data suggest that chronic moderate exercise can influence the inflammatory responses of macrophages by reprogramming their metabolic and epigenetic landscape.NEW & NOTEWORTHY In this study, we explain how long-term moderate exercise training can reduce inflammation in mouse macrophages by reprogramming the way they sense and respond to the presence of pathogens. We completed a thorough analysis and showed that these changes persist in macrophages because exercise improves the ability of cells to utilize oxygen without producing damaging compounds, and changes the way they access their DNA.
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