دورية أكاديمية
Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice.
| العنوان: | Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice. |
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| المؤلفون: | Ferreira TPT; Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Lima JGME; Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Farias-Filho FA; Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Jannini de Sá YAP; Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., de Arantes ACS; Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Guimarães FV; Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Carvalho VF; Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Hogaboam C; Department of Medicine, Cedars-Sinai Medical Center, Women's Guild Lung Institute, Los Angeles, CA, United States., Wallace J; Departments of Physiology and Pharmacology, and Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Martins MA; Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Silva PMRE; Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. |
| المصدر: | Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2020 Jun 17; Vol. 11, pp. 388. Date of Electronic Publication: 2020 Jun 17 (Print Publication: 2020). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101555782 Publication Model: eCollection Cited Medium: Print ISSN: 1664-2392 (Print) Linking ISSN: 16642392 NLM ISO Abbreviation: Front Endocrinol (Lausanne) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Anti-Inflammatory Agents/*administration & dosage , Fluocinolone Acetonide/*analogs & derivatives , Lung/*drug effects , Lung/*pathology , Pneumonia/*pathology , Silicon Dioxide/*toxicity , Silicosis/*pathology, Administration, Intranasal ; Animals ; Fibrosis/chemically induced ; Fibrosis/prevention & control ; Fluocinolone Acetonide/administration & dosage ; Male ; Mice ; Pneumonia/chemically induced ; Pneumonia/prevention & control ; Silicosis/complications ; Silicosis/prevention & control |
| مستخلص: | 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. (Copyright © 2020 Ferreira, Lima, Farias-Filho, Jannini de Sá, de Arantes, Guimarães, Carvalho, Hogaboam, Wallace, Martins and Silva.) |
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| معلومات مُعتمدة: | R01 HL123899 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: fibrosis; flunisolide; lung; silica particles; therapy |
| المشرفين على المادة: | 0 (Anti-Inflammatory Agents) 0CD5FD6S2M (Fluocinolone Acetonide) 7631-86-9 (Silicon Dioxide) 78M02AA8KF (flunisolide) |
| تواريخ الأحداث: | Date Created: 20200707 Date Completed: 20210513 Latest Revision: 20210901 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC7311565 |
| DOI: | 10.3389/fendo.2020.00388 |
| PMID: | 32625168 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-2392 |
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| DOI: | 10.3389/fendo.2020.00388 |