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=7

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=<sec id="ST1"><title>Introduction</title><p>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.</p></sec><sec id="ST2"><title>Methods</title><p>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), CysLT<sub>1</sub> receptor, CysLT<sub>2</sub> receptor, LTC4 synthase, and LTB4 receptor 2 (BLT2) were performed. Airway hyperresponsiveness (AHR) to methacholine (MCh) was assessed <italic>via</italic> whole body plethysmography.</p></sec><sec id="ST3"><title>Results</title><p>AE decreased eosinophils (<italic>p</italic> &lt; 0.001), neutrophils (<italic>p</italic> &gt; 0.001), lymphocytes (<italic>p</italic> &lt; 0.001), and macrophages (<italic>p</italic> &lt; 0.01) in BAL, as well as eosinophils (<italic>p</italic> &lt; 0.01), lymphocytes (<italic>p</italic> &lt; 0.001), and macrophages (<italic>p</italic> &gt; 0.001) in airway walls. Collagen (<italic>p</italic> &lt; 0.01), elastic fibers (<italic>p</italic> &lt; 0.01), mucus production (<italic>p</italic> &lt; 0.01), and smooth muscle thickness (<italic>p</italic> &lt; 0.01), as well as IL-5 (<italic>p</italic> &lt; 0.01), IL-13 (<italic>p</italic> &lt; 0.01), CysLT (<italic>p</italic> &lt; 0.01), and LTB4 (<italic>p</italic> &lt; 0.01) in BAL were reduced. 5-LO (<italic>p</italic> &lt; 0.05), LTA4H (<italic>p</italic> &lt; 0.05), CysLT<sub>1</sub> receptor (<italic>p</italic> &lt; 0.001), CysLT<sub>2</sub> receptor (<italic>p</italic> &lt; 0.001), LTC4 synthase (<italic>p</italic> &lt; 0.001), and BLT2 (<italic>p</italic> &lt; 0.01) expression by peribronchial leukocytes and airway epithelium were reduced. Lastly, AHR to MCh 25 mg/mL (<italic>p</italic> &lt; 0.05) and 50 mg/mL (<italic>p</italic> &lt; 0.01) was reduced.</p></sec><sec id="ST4"><title>Conclusion</title><p>Moderate-intensity AE attenuated asthma phenotype and LT production in both pulmonary leukocytes and airway epithelium of OVA-treated mice.</p></sec>