Exercise Reduces Lung Fibrosis Involving Serotonin/Akt Signaling.

Abstract

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.

• Authors: Paulo Rogerio Pereira, Manoel Carneiro Oliveira-Junior, Breanne Mackenzie, Jaime Eduardo Davino Chiovatto, Yves Matos, Flavia Regina Greiffo, Nicole Cristine Rigonato-Oliveira, Thayse Regina Brugemman, Humberto Delle, Marco Idzko, Regiane Albertini, Ana Paula Ligeiro Oliveira, Nilsa Regina Damaceno-Rodrigues, Elia Garcia Caldini, Isis Ensil Fernandez, Hugo Caire Castro-Faria-Neto, Marisa Dolhnikoff, Oliver Eickelberg, Rodolfo Paula Vieira
• Journal: Medicine and science in sports and exercise (Med Sci Sports Exerc) Vol. 48 Issue 7 Pg. 1276-84 (07 2016) ISSN: 1530-0315 [Electronic] United States
• PMID: 26895395 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Bleomycin
• Serotonin
• Proto-Oncogene Proteins c-akt

Topics

• 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