Aerobic Exercise Attenuated Bleomycin-Induced Lung Fibrosis in Th2-Dominant Mice

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Andrade-Sousa, Adilson Santos ; Pereira, Paulo Rogerio ; MacKenzie, BreAnne ; Oliveira-Junior, Manoel Carneiro ; Assumpcao-Neto, Erasmo ; Rodrigues Brandao-Rangel, Maysa Alves ; Damaceno-Rodrigues, Nilsa Regina ; Caldini, Elia Garcia ; Pereira Velosa, Ana Paula ; Teodoro, Walcy Rosolia ; Ligeiro de Oliveira, Ana Paula ; Dolhnikoff, Marisa ; Eickelberg, Oliver ; Vieira, Rodolfo Paula

• Document type: Journal article
• Source: PLoS One; v. 11, n. 9 SEP 27 2016.
• Web of Science Citations: 5

Abstract

Introduction The aim of this study was to investigate the effect of aerobic exercise (AE) in reducing bleomycin- induced fibrosis in mice of a Th2-dominant immune background (BALB/c). Methods BALB/c mice were distributed into: sedentary, control (CON), Exercise-only (EX), sedentary, bleomycin-treated (BLEO) and bleomycin-treated+exercised (BLEO+EX); (n = 8/group). Following treadmill adaptation, 15 days following a single, oro-tracheal administration of bleomycin (1.5U/kg), AE was performed 5 days/week, 60min/day for 4 weeks at moderate intensity (60% of maximum velocity reached during a physical test) and assessed for pulmonary inflammation and remodeling, and cytokine levels in bronchoalveolar lavage (BAL). Results At 45 days post injury, compared to BLEO, BLEO+EX demonstrated reduced collagen deposition in the airways (p<0.001) and also in the lung parenchyma (p<0.001). In BAL, a decreased number of total leukocytes (p<0.01), eosinophils (p<0.001), lymphocytes (p<0.01), macrophages (p<0.01), and neutrophils (p<0.01), as well as reduced pro-inflammatory cytokines (CXCL-1; p<0.01), (IL-1 beta; p<0.001), (IL-5; p<0.01), (IL-6; p<0.001), (IL-13; p<0.01) and pro-fibrotic growth factor IGF-1 (p<0.001) were observed. Anti-inflammatory cytokine IL-10 was increased (p<0.001). Conclusion AE attenuated bleomycin-induced collagen deposition, inflammation and cytokines accumulation in the lungs of mice with a predominately Th2-background suggesting that therapeutic AE (15-44 days post injury) attenuates the pro-inflammatory, Th2 immune response and fibrosis in the bleomycin model. (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: 14/14604-8 - 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: 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: 12/51464-4 - Effects of aerobic exercise on pulmonary fibrosis induced by bleomycin
• Grantee: Rodolfo de Paula Vieira
• Support Opportunities: Regular Research Grants