title: Elastase modifies bleomycin-induced pulmonary fibrosis in mice.
abstract: Pulmonary fibrosis (PF) is characterized by excessive accumulation of collagen in the lungs. Emphysema is characterized by loss of the extracellular matrix (ECM) and alveolar enlargement. We studied the co-participation of elastase-induced mild emphysema in bleomycin-induced PF in mice by analyzing oxidative stress, inflammation and lung histology. C57BL/6 mice were divided into four groups: control; bleomycin (0.1U/mouse); elastase (using porcine pancreatic elastase (PPE)+bleomycin (3U/mouse 14 days before 0.1U/mouse of bleomycin; PPE+B); elastase (3U/mouse). Mice were humanely sacrificed 7, 14 and 21 days after treatment with bleomycin or vehicle. PF was observed 14 days and 21 days after bleomycin treatment but was observed after 14 days only in the PPE+B group. In the PPE+B group at 21 days, we observed many alveoli and alveolar septa with few PF areas. We also observed marked and progressive increases of collagens 7, 14 and 21 days after bleomycin treatment whereas, in the PPE+B group, collagen deposition was observed only at 14 days. There was a reduction in activities of the antioxidant enzymes superoxide dismutase (p<0.05), catalase (p<0.01) and glutathione peroxidase (p<0.01) parallel with an increase in nitrite (p<0.01) 21 days after bleomycin treatment compared with the control group. These endpoints were also reduced (p<0.05, p<0.05 and p<0.01, respectively) and increased (p<0.01) in the PPE+B group at 21 days compared with the control group. Interleukin (IL)-1β expression was upregulated (p<0.01) whereas IL-6 was downregulated (p<0.05) in the PPE+B group at 21 days compared with the control group. PF and emphysema did not coexist in our model of lung disease and despite increased levels of oxidative stress and inflammatory markers after combined stimulus (elastase and bleomycin) overall histology was improved to that of the nearest control group.
authors: Pós-graduação em Biologia Humana e Experimental, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Brazil.
authors: Larissa Alexsandra Silva Neto
authors: LA
authors: Trajano
authors: Pós-graduação em Biologia Humana e Experimental, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Brazil.
authors: Eduardo Tavares Lima
authors: ET
authors: Trajano
authors: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil.
authors: Manuella
authors: M
authors: Lanzetti
authors: Pós-graduação em Imunologia e Inflamação, Instituto de Microbiologia Paulo de Goés, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Morena Scopel Amorim
authors: MS
authors: Mendonça
authors: Pós-graduação em Imunologia e Inflamação, Instituto de Microbiologia Paulo de Goés, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Rafael Freitas
authors: RF
authors: Guilherme
authors: Pós-graduação em Imunologia e Inflamação, Instituto de Microbiologia Paulo de Goés, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Rodrigo Tinoco
authors: RT
authors: Figueiredo
authors: Pós-graduação em Imunologia e Inflamação, Instituto de Microbiologia Paulo de Goés, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Cláudia Farias
authors: CF
authors: Benjamim
authors: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil. Electronic address: samuelv@ufrj.br.
authors: Samuel Santos
authors: SS
authors: Valenca
authors: Pós-graduação em Biologia Humana e Experimental, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Brazil.
authors: Andréa Monte Alto
authors: AM
authors: Costa
authors: Pós-graduação em Biologia Humana e Experimental, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Brazil.
authors: Luís Cristóvão
authors: LC
authors: Porto
mesh_terms: D000818:Animals; D001761:Bleomycin; D002374:Catalase / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D010196:Pancreatic Elastase / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D007378:Interleukins; D001761:Bleomycin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D010196:Pancreatic Elastase
keywords: Bleomycin; Elastase; Emphysema; Pulmonary fibrosis