Effects of aerobic exercise on molecular aspects of asthma: involvement of SOCS-JAK-STAT

Exerc Immunol Rev. 2019;25:50-62.


Background: Aerobic training (AT) decreases airway inflammation in asthma, but the underlying cellular and molecular mechanisms are not completely understood. Thus, this study evaluated the participation of SOCS-JAK-STAT signaling in the effects of AT on airway inflammation, remodeling and hyperresponsiveness in a model of allergic airway inflammation.

Methods: C57Bl/6 mice were divided into Control (Co), Exercise (Ex), HDM (HDM), and HDM+Exercise (HDM+ Ex). Dermatophagoides pteronyssinus (100ug/mouse) were administered oro-tracheally on days 0, 7, 14, 21, 28, 35, 42 and 49. AT was performed in a treadmill during 4 weeks in moderate intensity, from day 24 until day 52.

Results: AT inhibited HDM-induced total cells (p<0.001), eosinophils (p<0.01), neutrophils (p<0.01) and lymphocytes (p<0.01) in BAL, and eosinophils (p<0.01), neutrophils (p<0.01) and lymphocytes (p<0.01) in peribronchial space. AT also reduced BAL levels of IL-4 (p<0.001), IL-5 (p<0.001), IL-13 (p<0.001), CXCL1 (p<0.01), IL-17 (p<0.01), IL-23 (p<0.05), IL-33 (p<0.05), while increased IL- 10 (p<0.05). Airway collagen fibers (p<0.01), elastic fibers p<0.01) and mucin (p<0.01) were also reduced by AT. AT also inhibited HDM-induced airway hyperresponsiveness (AHR) to methacholine 6,25mg/ml (p<0.01), 12,5mg/mL (p<0.01), 25mg/mL (p<0.01) and 50mg/mL (p<0.01). Mechanistically, AT reduced the expression of STAT6 (p<0.05), STAT3 (p<0.001), STAT5 (p<0.01) and JAK2 (p<0.001), similarly by peribronchial leukocytes and by airway epithelial cells. SOCS1 expression (p<0.001) was upregulated in leukocytes and in epithelial cells, SOCS2 (p<0.01) was upregulated in leukocytes and SOCS3 down-regulated in leukocytes (p<0.05) and in epithelial cells (p<0.001).

Conclusions: AT reduces asthma phenotype involving SOCSJAK- STAT signaling.

Keywords: JAC; SOCS; STAT; asthma; exercise immunology.

MeSH terms

  • Animals
  • Asthma / metabolism*
  • Disease Models, Animal
  • Eosinophils / cytology
  • Interleukins / metabolism
  • Janus Kinases / metabolism*
  • Lymphocytes / cytology
  • Methacholine Chloride
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / cytology
  • Physical Conditioning, Animal*
  • Respiratory Hypersensitivity / metabolism
  • STAT Transcription Factors / metabolism*
  • Signal Transduction*
  • Suppressor of Cytokine Signaling Proteins / metabolism*


  • Interleukins
  • STAT Transcription Factors
  • Suppressor of Cytokine Signaling Proteins
  • Methacholine Chloride
  • Janus Kinases