AUTHOR=Alberca-Custódio Ricardo Wesley , Greiffo Flávia Regina , MacKenzie BreAnne , Oliveira-Junior Manoel Carneiro , Andrade-Sousa Adilson Santos , Graudenz Gustavo Silveira , Santos Angela Batista Gomes , Damaceno-Rodrigues Nilsa Regina , Castro-Faria-Neto Hugo Caire , Arantes-Costa Fernanda Magalhaes , Martins Milton De Arruda , Abbasi Asghar , Lin Chin Jia , Idzko Marco , Ligeiro Oliveira Ana Paula , Northoff Hinnak , Vieira Rodolfo Paula 

TITLE=Aerobic Exercise Reduces Asthma Phenotype by Modulation of the Leukotriene Pathway

JOURNAL=Frontiers in Immunology

VOLUME=Volume 7 - 2016

YEAR=2016

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00237

DOI=10.3389/fimmu.2016.00237

ISSN=1664-3224

ABSTRACT=Introduction: 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, 5x/week, 1hr/session for 4 weeks. Quantification of bronchoalveolar lavage (BAL) cellularity, leukocytes, airway remodeling, interleukin (IL) IL-5, IL-13, leukotriene Cys (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 to methacholine 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, airway hyperresponsiveness to methacholine 25mg/mL (p<0.05) and 50mg/mL (p<0.01) was reduced. Conclusions: Moderate intensity AE attenuated asthma phenotype and leukotriene production in both pulmonary leukocytes and airway epithelium of OVA-treated mice.