Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice
Silicosis is an occupational disease triggered by the inhalation of fine particles of crystalline silica and characterized by inflammation and scarring in the form of nodular lesions in the lungs. In spite of the therapeutic arsenal currently available, there is no specific treatment for the disease...
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| Format: | Article |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2020.00388/full |
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| author | Tatiana Paula Teixeira Ferreira Januário Gomes Mourão e Lima Francisco Alves Farias-Filho Yago Amigo Pinho Jannini de Sá Ana Carolina Santos de Arantes Fernanda Verdini Guimarães Vinicius de Frias Carvalho Cory Hogaboam John Wallace Marco Aurélio Martins Patrícia Machado Rodrigues e Silva |
| author_facet | Tatiana Paula Teixeira Ferreira Januário Gomes Mourão e Lima Francisco Alves Farias-Filho Yago Amigo Pinho Jannini de Sá Ana Carolina Santos de Arantes Fernanda Verdini Guimarães Vinicius de Frias Carvalho Cory Hogaboam John Wallace Marco Aurélio Martins Patrícia Machado Rodrigues e Silva |
| author_sort | Tatiana Paula Teixeira Ferreira |
| collection | DOAJ |
| description | Silicosis is an occupational disease triggered by the inhalation of fine particles of crystalline silica and characterized by inflammation and scarring in the form of nodular lesions in the lungs. In spite of the therapeutic arsenal currently available, there is no specific treatment for the disease. Flunisolide is a potent corticosteroid shown to be effective for controlling chronic lung inflammatory diseases. In this study, the effect of flunisolide on silica-induced lung pathological changes in mice was investigated. Swiss-Webster mice were injected intranasally with silica particles and further treated with flunisolide from day 21 to 27 post-silica challenge. Lung function was assessed by whole body invasive plethysmography. Granuloma formation was evaluated morphometrically, collagen deposition by Picrus sirius staining and quantitated by Sircol. Chemokines and cytokines were evaluated using enzyme-linked immunosorbent assay. The sensitivity of lung fibroblasts was also examined in in vitro assays. Silica challenge led to increased leukocyte numbers (mononuclear cells and neutrophils) as well as production of the chemokine KC/CXCL-1 and the cytokines TNF-α and TGF-β in the bronchoalveolar lavage. These alterations paralleled to progressive granuloma formation, collagen deposition and impairment of lung function. Therapeutic administration of intranasal flunisolide inhibited granuloma and fibrotic responses, noted 28 days after silica challenge. The upregulation of MIP-1α/CCL-3 and MIP-2/CXCL-2 and the cytokines TNF-α and TGF-β, as well as deposition of collagen and airway hyper-reactivity to methacholine were shown to be clearly sensitive to flunisolide, as compared to silica-challenge untreated mice. Additionally, flunisolide effectively suppressed the responses of proliferation and MCP-1/CCL-2 production from IL-13 stimulated lung fibroblasts from silica- or saline-challenged mice. In conclusion, we report that intranasal treatment with the corticosteroid flunisolide showed protective properties on pathological features triggered by silica particles in mice, suggesting that the compound may constitute a promising strategy for the treatment of silicosis. |
| first_indexed | 2024-12-11T21:23:41Z |
| format | Article |
| id | doaj.art-79323c491b6b427b873f736c1cd2efd8 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-11T21:23:41Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-79323c491b6b427b873f736c1cd2efd82022-12-22T00:50:23ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922020-06-011110.3389/fendo.2020.00388517109Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of MiceTatiana Paula Teixeira Ferreira0Januário Gomes Mourão e Lima1Francisco Alves Farias-Filho2Yago Amigo Pinho Jannini de Sá3Ana Carolina Santos de Arantes4Fernanda Verdini Guimarães5Vinicius de Frias Carvalho6Cory Hogaboam7John Wallace8Marco Aurélio Martins9Patrícia Machado Rodrigues e Silva10Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilDepartment of Medicine, Cedars-Sinai Medical Center, Women's Guild Lung Institute, Los Angeles, CA, United StatesDepartments of Physiology and Pharmacology, and Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, CanadaLaboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilSilicosis is an occupational disease triggered by the inhalation of fine particles of crystalline silica and characterized by inflammation and scarring in the form of nodular lesions in the lungs. In spite of the therapeutic arsenal currently available, there is no specific treatment for the disease. Flunisolide is a potent corticosteroid shown to be effective for controlling chronic lung inflammatory diseases. In this study, the effect of flunisolide on silica-induced lung pathological changes in mice was investigated. Swiss-Webster mice were injected intranasally with silica particles and further treated with flunisolide from day 21 to 27 post-silica challenge. Lung function was assessed by whole body invasive plethysmography. Granuloma formation was evaluated morphometrically, collagen deposition by Picrus sirius staining and quantitated by Sircol. Chemokines and cytokines were evaluated using enzyme-linked immunosorbent assay. The sensitivity of lung fibroblasts was also examined in in vitro assays. Silica challenge led to increased leukocyte numbers (mononuclear cells and neutrophils) as well as production of the chemokine KC/CXCL-1 and the cytokines TNF-α and TGF-β in the bronchoalveolar lavage. These alterations paralleled to progressive granuloma formation, collagen deposition and impairment of lung function. Therapeutic administration of intranasal flunisolide inhibited granuloma and fibrotic responses, noted 28 days after silica challenge. The upregulation of MIP-1α/CCL-3 and MIP-2/CXCL-2 and the cytokines TNF-α and TGF-β, as well as deposition of collagen and airway hyper-reactivity to methacholine were shown to be clearly sensitive to flunisolide, as compared to silica-challenge untreated mice. Additionally, flunisolide effectively suppressed the responses of proliferation and MCP-1/CCL-2 production from IL-13 stimulated lung fibroblasts from silica- or saline-challenged mice. In conclusion, we report that intranasal treatment with the corticosteroid flunisolide showed protective properties on pathological features triggered by silica particles in mice, suggesting that the compound may constitute a promising strategy for the treatment of silicosis.https://www.frontiersin.org/article/10.3389/fendo.2020.00388/fulllungfibrosissilica particlestherapyflunisolide |
| spellingShingle | Tatiana Paula Teixeira Ferreira Januário Gomes Mourão e Lima Francisco Alves Farias-Filho Yago Amigo Pinho Jannini de Sá Ana Carolina Santos de Arantes Fernanda Verdini Guimarães Vinicius de Frias Carvalho Cory Hogaboam John Wallace Marco Aurélio Martins Patrícia Machado Rodrigues e Silva Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice Frontiers in Endocrinology lung fibrosis silica particles therapy flunisolide |
| title | Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice |
| title_full | Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice |
| title_fullStr | Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice |
| title_full_unstemmed | Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice |
| title_short | Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice |
| title_sort | intranasal flunisolide suppresses pathological alterations caused by silica particles in the lungs of mice |
| topic | lung fibrosis silica particles therapy flunisolide |
| url | https://www.frontiersin.org/article/10.3389/fendo.2020.00388/full |
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