Exercise Reduces Lung Fibrosis Involving Serotonin/Akt Signaling

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Pereira, Paulo Rogerio ^[1] ; Oliveira-Junior, Manoel Carneiro ^[1] ; Mackenzie, Breanne ^[1] ; Davino Chiovatto, Jaime Eduardo ^[1] ; Matos, Yves ^[1] ; Greiffo, Flavia Regina ^[1] ; Rigonato-Oliveira, Nicole Cristine ^[1] ; Brugemman, Thayse Regina ^[2] ; Delle, Humberto ^[1] ; Idzko, Marco ^[3] ; Albertini, Regiane ^[1] ; Ligeiro Oliveira, Ana Paula ^[1] ; Damaceno-Rodrigues, Nilsa Regina ^[4] ; Caldini, Elia Garcia ^[4] ; Fernandez, Isis Ensil ^[5] ; Castro-Faria-Neto, Hugo Caire ^[6] ; Dolhnikoff, Marisa ^[7] ; Eickelberg, Oliver ^[5] ; Vieira, Rodolfo Paula ^[1]

Afiliação do(s) autor(es)

^[1] Nove de Julho Univ, Lab Pulm & Exercise Immunol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Lab Expt Therapeut, Sao Paulo - Brazil

^[3] Univ Hosp Freiburg, Dept Pneumol, COPD & Asthma Res Grp, Freiburg - Germany

^[4] Univ Sao Paulo, Sch Med, Lab Cellular Biol, Sao Paulo - Brazil

^[5] Univ Munich, Univ Hosp, Comprehens Pneumol Ctr, Munich - Germany

^[6] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Immunopharmacol, Rio De Janeiro - Brazil

^[7] Univ Sao Paulo, Sch Med, Dept Pathol, Lab Expt Air Pollut, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MEDICINE AND SCIENCE IN SPORTS AND EXERCISE; v. 48, n. 7, p. 1276-1284, JUL 2016.
• Citações Web of Science: 11

Resumo

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(-1)) was administered on day 1 and treadmill AT began on day 15 and continued for 60 min.d(-1), 5 d.wk(-1) for 4 wk. We evaluated total and differential cell counts in bronchoalveolar lavage (BAL), interleukin (IL)-1A, IL-6, CXCL1/KC, IL-10, tumor necrosis factor alpha, and transforming growth factor A 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-1A (P < 0.01), IL-6 (P < 0.05), CXCL1/KC (P < 0.001), tumor necrosis factor > (P < 0.001), and transforming growth factor A (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. (AU)

• Processo FAPESP: 12/15165-2 - Papel da sinalização purinérgica e da sinalização SOCS-JAK-STAT nos efeitos antiinflamatórios do treinamento aeróbio em modelos experimentais de asma e em indivíduos asmáticos
• Beneficiário: Rodolfo de Paula Vieira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 14/23196-0 - Papel da sinalização purinérgica e da sinalização SOCS-JAK-STAT nos efeitos anti-inflamatórios do treinamento aeróbio em indivíduos asmáticos
• Beneficiário: Breanne Mackenzie
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/14604-8 - Papel da sinalização purinérgica nos efeitos anti-inflamatórios do treinamento aeróbio em um modelo de asma induzida por ácaro de poeira doméstica
• Beneficiário: Manoel Carneiro de Oliveira Junior
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/51464-4 - Effects of aerobic exercise on pulmonary fibrosis induced by bleomycin
• Beneficiário: Rodolfo de Paula Vieira
• Modalidade de apoio: Auxílio à Pesquisa - Regular