title: Aerobic Exercise Reduces Asthma Phenotype by Modulation of the Leukotriene Pathway.
abstract: BACKGROUND
  Leukotrienes (LTs) play a central role in asthma. Low- to moderate-intensity aerobic exercise (AE) reduces asthmatic inflammation in clinical studies and in experimental models. This study investigated whether AE attenuates LT pathway activation in an ovalbumin (OVA) model of asthma.
  
  
  METHODS
  Sixty-four male, BALB/c mice were distributed into Control, Exercise (Exe), OVA, and OVA + Exe groups. Treadmill training was performed at moderate intensity, 5×/week, 1 h/session for 4 weeks. Quantification of bronchoalveolar lavage (BAL) cellularity, leukocytes, airway remodeling, interleukin (IL)-5, IL-13, cysteinyl leukotriene (CysLT), and leukotriene B4 (LTB4) in BAL was performed. In addition, quantitative analyses on peribronchial leukocytes and airway epithelium for LT pathway agents: 5-lypoxygenase (5-LO), LTA4 hydrolase (LTA4H), CysLT1 receptor, CysLT2 receptor, LTC4 synthase, and LTB4 receptor 2 (BLT2) were performed. Airway hyperresponsiveness (AHR) to methacholine (MCh) was assessed via whole body plethysmography.
  
  
  RESULTS
  AE decreased eosinophils (p < 0.001), neutrophils (p > 0.001), lymphocytes (p < 0.001), and macrophages (p < 0.01) in BAL, as well as eosinophils (p < 0.01), lymphocytes (p < 0.001), and macrophages (p > 0.001) in airway walls. Collagen (p < 0.01), elastic fibers (p < 0.01), mucus production (p < 0.01), and smooth muscle thickness (p < 0.01), as well as IL-5 (p < 0.01), IL-13 (p < 0.01), CysLT (p < 0.01), and LTB4 (p < 0.01) in BAL were reduced. 5-LO (p < 0.05), LTA4H (p < 0.05), CysLT1 receptor (p < 0.001), CysLT2 receptor (p < 0.001), LTC4 synthase (p < 0.001), and BLT2 (p < 0.01) expression by peribronchial leukocytes and airway epithelium were reduced. Lastly, AHR to MCh 25 mg/mL (p < 0.05) and 50 mg/mL (p < 0.01) was reduced.
  
  
  CONCLUSIONS
  Moderate-intensity AE attenuated asthma phenotype and LT production in both pulmonary leukocytes and airway epithelium of OVA-treated mice.
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE) , São Paulo , Brazil.
authors.forename: Ricardo Wesley
authors.initials: RW
authors.lastname: Alberca-Custódio
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE) , São Paulo , Brazil.
authors.forename: Flávia Regina
authors.initials: FR
authors.lastname: Greiffo
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE) , São Paulo , Brazil.
authors.forename: BreAnne
authors.initials: B
authors.lastname: MacKenzie
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE) , São Paulo , Brazil.
authors.forename: Manoel Carneiro
authors.initials: MC
authors.lastname: Oliveira-Junior
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE) , São Paulo , Brazil.
authors.forename: Adilson Santos
authors.initials: AS
authors.lastname: Andrade-Sousa
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE) , São Paulo , Brazil.
authors.forename: Gustavo Silveira
authors.initials: GS
authors.lastname: Graudenz
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE) , São Paulo , Brazil.
authors.forename: Angela Batista Gomes
authors.initials: AB
authors.lastname: Santos
authors.affiliation: Laboratory of Cellular Biology (LIM 59), School of Medicine, University of São Paulo (USP) , São Paulo , Brazil.
authors.forename: Nilsa Regina
authors.initials: NR
authors.lastname: Damaceno-Rodrigues
authors.affiliation: Laboratory of Immunopharmacology, Institute Oswaldo Cruz (IOF), Oswaldo Cruz Foundation , Rio de Janeiro , Brazil.
authors.forename: Hugo Caire
authors.initials: HC
authors.lastname: Castro-Faria-Neto
authors.affiliation: Laboratory of Experimental Therapeutics (LIM 20), School of Medicine, University of São Paulo (USP) , São Paulo , Brazil.
authors.forename: Fernanda Magalhaes
authors.initials: FM
authors.lastname: Arantes-Costa
authors.affiliation: Laboratory of Experimental Therapeutics (LIM 20), School of Medicine, University of São Paulo (USP) , São Paulo , Brazil.
authors.forename: Milton De Arruda
authors.initials: Mde A
authors.lastname: Martins
authors.affiliation: Institute for Memory Impairments and Neurological Disorders (MIND Institute), University of California Irvine , Irvine, CA , USA.
authors.forename: Asghar
authors.initials: A
authors.lastname: Abbasi
authors.affiliation: Department of Pathology (LIM 05), School of Medicine, University of São Paulo (USP) , São Paulo , Brazil.
authors.forename: Chin Jia
authors.initials: CJ
authors.lastname: Lin
authors.affiliation: COPD and Asthma Research Group, Department of Pneumology, University Hospital Freiburg , Freiburg , Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Idzko
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE) , São Paulo , Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ligeiro Oliveira
authors.affiliation: Institute of Clinical and Experimental Transfusion Medicine (IKET), University of Tübingen , Tübingen , Germany.
authors.forename: Hinnak
authors.initials: H
authors.lastname: Northoff
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE) , São Paulo , Brazil.
authors.forename: Rodolfo Paula
authors.initials: RP
authors.lastname: Vieira
keywords: airway inflammation; asthma; cytokines; exercise immunology; leukotrienes