A R Almeida-Oliveira1, Jcj Aquino-Junior1, A Abbasi2, A Santos-Dias3, M C Oliveira-Junior3, R W Alberca-Custodio3, N C Rigonato-Oliveira4, L P Salles-Dias5, N R Damaceno-Rodrigues6, E G Caldini6, F M Arantes-Costa7, A P Ligeiro-Oliveira4, M G Belvisi8, R P Vieira9. 1. Nove de Julho University, Rua Vergueiro 235/249, Liberdade, São Paulo - SP, Brazil, 01504-001. Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Rua Pedro Ernesto 240, São José dos Campos - SP, Brazil, 12245-520. 2. Division of Respiratory & Critical Care Physiology & Medicine, Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA. 3. Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Rua Pedro Ernesto 240, São José dos Campos - SP, Brazil, 12245-520. 4. Nove de Julho University, Rua Vergueiro 235/249, Liberdade, São Paulo - SP, Brazil, 01504-001. 5. Universidade Brasil, Post-graduation Program in Bioengineering and in Biomedical Engineering, Campus Itaquera, Rua Carolina Fonseca 235, São Paulo - SP, Brazil, 08230-030. 6. University of Sao Paulo, School of Medicine, Department of Pathology, Laboratory of Cell Biology (LIM 59), Avenida Doutor Arnaldo 455, Cerqueira Cesar, São Paulo - SP, Brazil, 01246-903. 7. University of Sao Paulo, School of Medicine, Department of Clinical Medicine, Laboratory of Experimental Therapeutics (LIM 20), Avenida Doutor Arnaldo 455, Cerqueira Cesar, São Paulo - SP, Brazil, 01246-903. 8. Respiratory Pharmacology Group, Airway Disease, National Heart and Lung Institute, Imperial College London, London, UK. 9. Universidade Brasil, Post-graduation Program in Bioengineering and in Biomedical Engineering, Campus Itaquera, Rua Carolina Fonseca 235, São Paulo - SP, Brazil, 08230-030. Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Rua Pedro Ernesto 240, São José dos Campos - SP, Brazil, 12245-520. Post-Graduation Program in Sciences of Human Movement and Rehabilitation, Federal University of Sao Paulo (UNIFESP), Campus Baixada Santista, Av. Ana Costa, 95 - Vila Mathias - Santos/SP - CEP: 11060-001.
Abstract
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.
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.
Authors: J L Carvalho; M Miranda; A K Fialho; H Castro-Faria-Neto; E Anatriello; A C Keller; F Aimbire Journal: PLoS One Date: 2020-04-24 Impact factor: 3.240