PMID- 37306389
OWN - NLM
STAT- MEDLINE
DCOM- 20230725
LR  - 20230803
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 325
IP  - 2
DP  - 2023 Aug 1
TI  - Moderate exercise induces trained immunity in macrophages.
PG  - C429-C442
LID - 10.1152/ajpcell.00130.2023 [doi]
AB  - 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-kappaB 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.
FAU - Murugathasan, Mayoorey
AU  - Murugathasan M
AD  - School of Kinesiology and Health Science, Muscle Health Research Centre, York 
      University, Toronto, Ontario, Canada.
FAU - Jafari, Ardavan
AU  - Jafari A
AD  - School of Kinesiology and Health Science, Muscle Health Research Centre, York 
      University, Toronto, Ontario, Canada.
FAU - Amandeep, Amandeep
AU  - Amandeep A
AD  - School of Kinesiology and Health Science, Muscle Health Research Centre, York 
      University, Toronto, Ontario, Canada.
FAU - Hassan, Syed A
AU  - Hassan SA
AD  - School of Kinesiology and Health Science, Muscle Health Research Centre, York 
      University, Toronto, Ontario, Canada.
FAU - Chihata, Matthew
AU  - Chihata M
AD  - School of Kinesiology and Health Science, Muscle Health Research Centre, York 
      University, Toronto, Ontario, Canada.
FAU - Abdul-Sater, Ali A
AU  - Abdul-Sater AA
AUID- ORCID: 0000-0002-0022-0930
AD  - School of Kinesiology and Health Science, Muscle Health Research Centre, York 
      University, Toronto, Ontario, Canada.
LA  - eng
SI  - figshare/10.6084/m9.figshare.22568293
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230612
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Chromatin)
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - *Trained Immunity
MH  - *Macrophages/metabolism
MH  - Inflammation/metabolism
MH  - Signal Transduction
MH  - Chromatin/metabolism
MH  - Lipopolysaccharides/pharmacology
OTO - NOTNLM
OT  - epigenetic
OT  - exercise
OT  - inflammation
OT  - macrophages
OT  - mitochondria
EDAT- 2023/06/12 13:06
MHDA- 2023/07/25 06:42
CRDT- 2023/06/12 08:43
PHST- 2023/07/25 06:42 [medline]
PHST- 2023/06/12 13:06 [pubmed]
PHST- 2023/06/12 08:43 [entrez]
AID - 10.1152/ajpcell.00130.2023 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2023 Aug 1;325(2):C429-C442. doi: 
      10.1152/ajpcell.00130.2023. Epub 2023 Jun 12.