Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/14422 |
Resumo: | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. |
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Cruz, Fernanda FerreiraHorta, Lucas Felipe BastosMaia, Lígia de AlbuquerqueLopes-Pacheco, MiquéiasSilva, André Benedito daMorales, Marcelo MarcoGonçalves-de-Albuquerque, Cassiano FelippeTakiya, Christina MaedaFaria Neto, Hugo Caire de CastroRocco, Patricia Rieken Macedo2016-06-02T13:05:21Z2016-06-03T12:34:15Z2016-06-02T13:05:21Z2016-06-03T12:34:15Z2016CRUZ, Fernanda Ferreira; et al. Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis. Plos One, v.11, n.1, 17p, Jan. 2016.1932-6203https://www.arca.fiocruz.br/handle/icict/1442210.1371/journal.pone.0147005engPublic Library of ScienceDasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Fisiologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Fisiologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Fisiologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Patologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil.Silicosis is an occupational lung disease with no effective treatment. We hypothesized that dasatinib, a tyrosine kinase inhibitor, might exhibit therapeutic efficacy in silica-induced pulmonary fibrosis. Silicosis was induced in C57BL/6 mice by a single intratracheal administration of silica particles, whereas the control group received saline. After 14 days, when the disease was already established, animals were randomly assigned to receive DMSO or dasatinib (1 mg/kg) by oral gavage, twice daily, for 14 days. On day 28, lung morphofunction, inflammation, and remodeling were investigated. RAW 264.7 cells (a macrophage cell line) were incubated with silica particles, followed by treatment or not with dasatinib, and evaluated for macrophage polarization. On day 28, dasatinib improved lung mechanics, increased M2 macrophage counts in lung parenchyma and granuloma, and was associated with reduction of fraction area of granuloma, fraction area of collapsed alveoli, protein levels of tumor necrosis factor-α, interleukin-1β, transforming growth factor-β, and reduced neutrophils, M1 macrophages, and collagen fiber content in lung tissue and granuloma in silicotic animals. Additionally, dasatinib reduced expression of iNOS and increased expression of arginase and metalloproteinase-9 in silicotic macrophages. Dasatinib was effective at inducing macrophage polarization toward the M2 phenotype and reducing lung inflammation and fibrosis, thus improving lung mechanics in a murine model of acute silicosis.SilicosisLung InflammationFibrosisDasatinibAcute Experimental SilicosisSilicosePneumoniaFibroseDasatinibeinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALcassiano_albuquerque_etal_IOC_2016.PDFapplication/pdf9843117https://www.arca.fiocruz.br/bitstream/icict/14422/1/cassiano_albuquerque_etal_IOC_2016.PDF665abfe6c111cd9eb3f1730cf432ebfeMD51LICENSElicense.txttext/plain2991https://www.arca.fiocruz.br/bitstream/icict/14422/2/license.txt5a560609d32a3863062d77ff32785d58MD52TEXTcassiano_albuquerque_etal_IOC_2016.PDF.txtcassiano_albuquerque_etal_IOC_2016.PDF.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis |
| title |
Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis |
| spellingShingle |
Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis Cruz, Fernanda Ferreira Silicosis Lung Inflammation Fibrosis Dasatinib Acute Experimental Silicosis Silicose Pneumonia Fibrose Dasatinibe |
| title_short |
Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis |
| title_full |
Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis |
| title_fullStr |
Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis |
| title_full_unstemmed |
Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis |
| title_sort |
Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis |
| author |
Cruz, Fernanda Ferreira |
| author_facet |
Cruz, Fernanda Ferreira Horta, Lucas Felipe Bastos Maia, Lígia de Albuquerque Lopes-Pacheco, Miquéias Silva, André Benedito da Morales, Marcelo Marco Gonçalves-de-Albuquerque, Cassiano Felippe Takiya, Christina Maeda Faria Neto, Hugo Caire de Castro Rocco, Patricia Rieken Macedo |
| author_role |
author |
| author2 |
Horta, Lucas Felipe Bastos Maia, Lígia de Albuquerque Lopes-Pacheco, Miquéias Silva, André Benedito da Morales, Marcelo Marco Gonçalves-de-Albuquerque, Cassiano Felippe Takiya, Christina Maeda Faria Neto, Hugo Caire de Castro Rocco, Patricia Rieken Macedo |
| author2_role |
author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Cruz, Fernanda Ferreira Horta, Lucas Felipe Bastos Maia, Lígia de Albuquerque Lopes-Pacheco, Miquéias Silva, André Benedito da Morales, Marcelo Marco Gonçalves-de-Albuquerque, Cassiano Felippe Takiya, Christina Maeda Faria Neto, Hugo Caire de Castro Rocco, Patricia Rieken Macedo |
| dc.subject.en.pt_BR.fl_str_mv |
Silicosis Lung Inflammation Fibrosis Dasatinib Acute Experimental Silicosis |
| topic |
Silicosis Lung Inflammation Fibrosis Dasatinib Acute Experimental Silicosis Silicose Pneumonia Fibrose Dasatinibe |
| dc.subject.decs.pt_BR.fl_str_mv |
Silicose Pneumonia Fibrose Dasatinibe |
| description |
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. |
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2016 |
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2016-06-02T13:05:21Z 2016-06-03T12:34:15Z |
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2016-06-02T13:05:21Z 2016-06-03T12:34:15Z |
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2016 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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CRUZ, Fernanda Ferreira; et al. Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis. Plos One, v.11, n.1, 17p, Jan. 2016. |
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https://www.arca.fiocruz.br/handle/icict/14422 |
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1932-6203 |
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10.1371/journal.pone.0147005 |
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CRUZ, Fernanda Ferreira; et al. Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis. Plos One, v.11, n.1, 17p, Jan. 2016. 1932-6203 10.1371/journal.pone.0147005 |
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