Science and Research

Exercise Reduces Lung Fibrosis Involving Serotonin/Akt Signaling

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)-1beta, IL-6, CXCL1/KC, IL-10, tumor necrosis factor alpha, and transforming growth factor beta 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-1beta (P < 0.01), IL-6 (P < 0.05), CXCL1/KC (P < 0.001), tumor necrosis factor alpha (P < 0.001), and transforming growth factor beta (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.
  • Pereira, P. R.
  • Oliveira-Junior, M. C.
  • Mackenzie, B.
  • Chiovatto, J. E.
  • 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.

Keywords

  • 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/metabolism/*therapy
  • Serotonin/*metabolism
  • *Signal Transduction
Publication details
DOI: 10.1249/MSS.0000000000000907
Journal: Med Sci Sports Exerc
Pages: 1276-84 
Number: 7
Work Type: Original
Location: CPC-M
Disease Area: DPLD
Partner / Member: HMGU
Access-Number: 26895395
See publication on PubMed

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