title: Exercise Reduces Lung Fibrosis Involving Serotonin/Akt Signaling.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: 1Laboratory of Pulmonary and Exercise Immunology, Nove de Julho University, São Paulo, BRAZIL; 2Laboratory of Experimental Therapeutics, School of Medicine, University of São Paulo, São Paulo, BRAZIL; 3COPD and Asthma Research Group, Department of Pneumology, University Hospital Freiburg, Freiburg, GERMANY; 4Laboratory of Cellular Biology, School of Medicine, University of Sao Paulo, São Paulo, BRAZIL; 5Comprehensive Pneumology Centre, University Hospital of the Ludwig Maximilians University Munich, Munich, GERMANY; 6Laboratory of Immunopharmacology, Institute Oswaldo Cruz, Oswaldo Cruz Foundation, Rio de Janeiro, BRAZIL; and 7Laboratory of Experimental Air Pollution, Department of Pathology, School of Medicine, University of Sao Paulo, São Paulo, BRAZIL.
authors.forename: Paulo Rogerio
authors.initials: PR
authors.lastname: Pereira
authors.forename: Manoel Carneiro
authors.initials: MC
authors.lastname: Oliveira-Junior
authors.forename: Breanne
authors.initials: B
authors.lastname: Mackenzie
authors.forename: Jaime Eduardo Davino
authors.initials: JE
authors.lastname: Chiovatto
authors.forename: Yves
authors.initials: Y
authors.lastname: Matos
authors.forename: Flavia Regina
authors.initials: FR
authors.lastname: Greiffo
authors.forename: Nicole Cristine
authors.initials: NC
authors.lastname: Rigonato-Oliveira
authors.forename: Thayse Regina
authors.initials: TR
authors.lastname: Brugemman
authors.forename: Humberto
authors.initials: H
authors.lastname: Delle
authors.forename: Marco
authors.initials: M
authors.lastname: Idzko
authors.forename: Regiane
authors.initials: R
authors.lastname: Albertini
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ligeiro Oliveira
authors.forename: Nilsa Regina
authors.initials: NR
authors.lastname: Damaceno-Rodrigues
authors.forename: Elia Garcia
authors.initials: EG
authors.lastname: Caldini
authors.forename: Isis Ensil
authors.initials: IE
authors.lastname: Fernandez
authors.forename: Hugo Caire
authors.initials: HC
authors.lastname: Castro-Faria-Neto
authors.forename: Marisa
authors.initials: M
authors.lastname: Dolhnikoff
authors.forename: Oliver
authors.initials: O
authors.lastname: Eickelberg
authors.forename: Rodolfo Paula
authors.initials: RP
authors.lastname: Vieira
mesh_terms: D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D005080:Exercise Test; D008297:Male; D008810:Mice, Inbred C57BL; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D001761:Bleomycin; D012701:Serotonin; D051057:Proto-Oncogene Proteins c-akt