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