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Pereira, P.R.* ; Oliveira-Junior, M.C.* ; MacKenzie, B.* ; Chiovatto, J.E.D.* ; Matos, Y.* ; Greiffo, F.R.* ; Rigonato-Oliveira, N.C.* ; Brugemman, T.R.* ; Delle, H.* ; Idzko, M.* ; Albertini, R.* ; Ligeiro Oliveira, A.P.* ; Damaceno-Rodrigues, N.R.* ; Caldini, E.G.* ; Fernandez, I.E. ; Castro-Faria-Neto, H.C.* ; Dolhnikoff, M.* ; Eickelberg, O. ; Vieira, R.P.*

Exercise reduces lung fibrosis involving serotonin/akt signaling.

Med. Sci. Sports Exerc. 48, 1276-1284 (2016)
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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) 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. 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-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. 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.  
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0025-7990
e-ISSN 1530-0315
Quellenangaben Volume: 48, Issue: 7, Pages: 1276-1284 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Reviewing status Peer reviewed