Exercise Reduces Lung Fibrosis Involving Serotonin/Akt Signaling

• Published in: Medicine and science in sports and exercise Vol. 48; no. 7; p. 1276
• Main Authors: Pereira, Paulo Rogerio, Oliveira-Junior, Manoel Carneiro, Mackenzie, Breanne, Chiovatto, Jaime Eduardo Davino, Matos, Yves, Greiffo, Flavia Regina, Rigonato-Oliveira, Nicole Cristine, Brugemman, Thayse Regina, Delle, Humberto, Idzko, Marco, Albertini, Regiane, Ligeiro Oliveira, Ana Paula, Damaceno-Rodrigues, Nilsa Regina, Caldini, Elia Garcia, Fernandez, Isis Ensil, Castro-Faria-Neto, Hugo Caire, Dolhnikoff, Marisa, Eickelberg, Oliver, Vieira, Rodolfo Paula
• Format: Journal Article
• Language: English
• Published: United States 01.07.2016
• Subjects: Animals; Bleomycin; Bronchoalveolar Lavage Fluid; Cytokines - metabolism; Exercise Test; Male; Mice, Inbred C57BL; Physical Conditioning, Animal; Proto-Oncogene Proteins c-akt - metabolism; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - therapy; Serotonin - metabolism; Signal Transduction
• ISSN: 1530-0315
• DOI: 10.1249/MSS.0000000000000907

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia, which involves aberrant serotonin (5-hydroxytryptamine [5-HT]) and Akt signaling. As protective effects of chronic aerobic training (AT) have been demonstrated in the context of lung injury, this study investigated whether AT attenuates bleomycin-induced lung fibrosis partly via a reduction of 5-HT and AKT signaling. Seventy-two C57BL/6 male mice were distributed in Control (Co), Exercise (Ex), Fibrosis (Fi), and Fibrosis + Exercise (Fi + Ex) groups. Bleomycin (1.5 UI·kg) was administered on day 1 and treadmill AT began on day 15 and continued for 60 min·d, 5 d·wk for 4 wk. We evaluated total and differential cell counts in bronchoalveolar lavage (BAL), interleukin (IL)-1β, IL-6, CXCL1/KC, IL-10, tumor necrosis factor α, and transforming growth factor β levels in BAL, collagen content in lung parenchyma, 5-HT levels in BAL fluid and in serum, the expression of 5-HT2B receptor, and Akt phosphorylation in lung tissue. AT reduced bleomycin-increased number of total cells (P < 0.001), neutrophils (P < 0.01), macrophages (P < 0.01), and lymphocytes (P < 0.05) in BAL. It also reduced the levels of IL-1β (P < 0.01), IL-6 (P < 0.05), CXCL1/KC (P < 0.001), tumor necrosis factor α (P < 0.001), and transforming growth factor β (P < 0.001). It increased expression of ant-inflammatory cytokine IL-10 (P < 0.001). It reduced bleomycin-increased 5-HT levels in BAL (P < 0.001) and in serum (P < 0.05). Reductions in collagen fiber deposition (P < 0.01), 5-HT2B receptor expression (P < 0.01), and Akt phosphorylation in lung tissue were observed. AT accelerates the resolution of lung inflammation and fibrosis in a model of bleomycin-induced lung fibrosis partly via attenuation of 5-HT/Akt signaling.