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Pereira, Paulo Rogerio; Oliveira-Junior, Manoel Carneiro; Mackenzie, Breanne; Davino Chiovatto, Jaime Eduardo; 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 (2016): Exercise Reduces Lung Fibrosis Involving Serotonin/Akt Signaling. In: Medicine and Science in Sports and Exercise, Vol. 48, No. 7: pp. 1276-1284
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Purpose: 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. Methods: 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(-1)) was administered on day 1 and treadmill AT began on day 15 and continued for 60 min.d(-1), 5 d.wk(-1) for 4 wk. We evaluated total and differential cell counts in bronchoalveolar lavage (BAL), interleukin (IL)-1A, IL-6, CXCL1/KC, IL-10, tumor necrosis factor alpha, and transforming growth factor A 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. Results: 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-1A (P < 0.01), IL-6 (P < 0.05), CXCL1/KC (P < 0.001), tumor necrosis factor > (P < 0.001), and transforming growth factor A (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. Conclusions: 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.