Dataset Information

Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis.

ABSTRACT: 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-?, interleukin-1?, transforming growth factor-?, 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.

SUBMITTER: Cruz FF

PROVIDER: S-EPMC4720427 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis.

Cruz Fernanda Ferreira FF Horta Lucas Felipe Bastos LF Maia Lígia de Albuquerque Lde A Lopes-Pacheco Miquéias M da Silva André Benedito AB Morales Marcelo Marco MM Gonçalves-de-Albuquerque Cassiano Felippe CF Takiya Christina Maeda CM de Castro-Faria-Neto Hugo Caire HC Rocco Patricia Rieken Macedo PR

PloS one 20160120 1

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 dai ...[more]

PMID: 26789403

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Dataset Information

Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis.

Publications

Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis.

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