Aerobic Exercise Reduces Asthma Phenotype by Modulation of the Leukotriene Pathway

Author(s):Show less -

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]}

Affiliation

^[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

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 7, JUN 14 2016.
• Web of Science Citations: 9

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, 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. (AU)

• FAPESP's process: 12/15165-2 - Role of purinergic signaling and of SOCS-JAK-STAT signaling in the antiinflammatory effects of aerobic training in experimental models of asma and in asthmatic individuals
• Grantee: Rodolfo de Paula Vieira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 14/23196-0 - The role of purinergic signalling and of SOCS-JAK-STAT signalling in the anti-inflammatory effects of aerobic training in asthmatic individuals.
• Grantee: Breanne Mackenzie
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/23763-0 - The role of airway epithelial cells on experimental models of asthma
• Grantee: Flavia Regina Greiffo
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• FAPESP's process: 12/23305-9 - Effects of aerobic physical training on the chronic allergic pulmonary inflammation in mice: role of purinergic signaling
• Grantee: Flavia Regina Greiffo
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/14604-8 - Role of purinergic signaling in the antiinflammatory effects of aerobic training in a model of asthma induced by house dust mite
• Grantee: Manoel Carneiro de Oliveira Junior
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/21519-1 - Is the leukotrienes via contributes to the anti-inflammatory effects of aerobic exercise in asthma?
• Grantee: Ricardo Wesley Alberca Custódio
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/09292-7 - Application of in vivo imaging, a central technique for pre-clinical studies, in a model of pulmonary fibrosis
• Grantee: Ricardo Wesley Alberca Custódio
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree