Aerobic Exercise Reduces Asthma Phenotype by Modulation of the Leukotriene Pathway

被引:25
作者
Alberca-Custodio, Ricardo Wesley [1 ,2 ]
Greiffo, Flavia Regina [1 ,2 ]
MacKenzie, BreAnne [1 ,2 ]
Oliveira-Junior, Manoel Carneiro [1 ,2 ]
Andrade-Sousa, Adilson Santos [1 ,2 ]
Graudenz, Gustavo Silveira [1 ,2 ]
Gomes Santos, Angela Batista [1 ,2 ]
Damaceno-Rodrigues, Nilsa Regina [3 ]
Castro-Faria-Neto, Hugo Caire [4 ]
Arantes-Costa, Fernanda Magalhaes [5 ]
Martins, Milton De Arruda [5 ]
Abbasi, Asghar [6 ]
Lin, Chin Jia [7 ]
Idzko, Marco [8 ]
Ligeiro Oliveira, Ana Paula [1 ,2 ]
Northoff, Hinnak [9 ]
Vieira, Rodolfo Paula [1 ,2 ]
机构
[1] Nove de Julho Univ UNINOVE, Lab Pulm & Exercise Immunol LABPEI, Sao Paulo, Brazil
[2] Nove de Julho Univ UNINOVE, Brazilian Inst Teaching & Res Pulm & Exercise Imm, Sao Paulo, Brazil
[3] Univ Sao Paulo, Sch Med, Lab Cellular Biol LIM 59, BR-09500900 Sao Paulo, Brazil
[4] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz IOF, Lab Immunopharmacol, Rio De Janeiro, Brazil
[5] Univ Sao Paulo, Sch Med, Lab Expt Therapeut LIM 20, BR-09500900 Sao Paulo, Brazil
[6] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders, MIND Inst, Irvine, CA USA
[7] Univ Sao Paulo, Dept Pathol LIM 05, Sch Med, BR-09500900 Sao Paulo, Brazil
[8] Univ Hosp Freiburg, Dept Pneumol, COPD & Asthma Res Grp, Freiburg, Germany
[9] Univ Tubingen, Inst Clin & Expt Transfus Med IKET, Tubingen, Germany
来源
FRONTIERS IN IMMUNOLOGY | 2016年 / 7卷
基金
巴西圣保罗研究基金会;
关键词
airway inflammation; asthma; cytokines; exercise immunology; leukotrienes; RANDOMIZED CONTROLLED-TRIAL; ALLERGIC LUNG INFLAMMATION; INDUCED BRONCHOCONSTRICTION; AIRWAY INFLAMMATION; ANIMAL-MODELS; MURINE MODEL; MODERATE; CELLS; MONTELUKAST; MECHANISMS;
D O I
10.3389/fimmu.2016.00237
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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, 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(1) receptor, CysLT(2) 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), CysLT(1) receptor (p < 0.001), CysLT(2) 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. Conclusion: Moderate-intensity AE attenuated asthma phenotype and LT production in both pulmonary leukocytes and airway epithelium of OVA-treated mice.
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页数:9
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