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Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1

BACKGROUND: Inhalation of dust containing silica particles is associated with severe pulmonary inflammation and lung injury leading to chronic silicosis including fibrotic remodeling of the lung. Silicosis represents a major global health problem causing more than 45.000 deaths per year. The inflamm...

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Autores principales: Peukert, Konrad, Steinhagen, Folkert, Fox, Mario, Feuerborn, Caroline, Schulz, Susanne, Seeliger, Benjamin, Schuss, Patrick, Schneider, Matthias, Frede, Stilla, Sauer, Andrea, Putensen, Christian, Latz, Eicke, Wilhelm, Christoph, Bode, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822850/
https://www.ncbi.nlm.nih.gov/pubmed/35130879
http://dx.doi.org/10.1186/s12931-022-01937-7
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author Peukert, Konrad
Steinhagen, Folkert
Fox, Mario
Feuerborn, Caroline
Schulz, Susanne
Seeliger, Benjamin
Schuss, Patrick
Schneider, Matthias
Frede, Stilla
Sauer, Andrea
Putensen, Christian
Latz, Eicke
Wilhelm, Christoph
Bode, Christian
author_facet Peukert, Konrad
Steinhagen, Folkert
Fox, Mario
Feuerborn, Caroline
Schulz, Susanne
Seeliger, Benjamin
Schuss, Patrick
Schneider, Matthias
Frede, Stilla
Sauer, Andrea
Putensen, Christian
Latz, Eicke
Wilhelm, Christoph
Bode, Christian
author_sort Peukert, Konrad
collection PubMed
description BACKGROUND: Inhalation of dust containing silica particles is associated with severe pulmonary inflammation and lung injury leading to chronic silicosis including fibrotic remodeling of the lung. Silicosis represents a major global health problem causing more than 45.000 deaths per year. The inflammasome-caspase-1 pathway contributes to the development of silica-induced inflammation and fibrosis via IL-1β and IL-18 production. Recent studies indicate that tetracycline can be used to treat inflammatory diseases mediated by IL-1β and IL-18. Therefore, we hypothesized that tetracycline reduces silica-induced lung injury and lung fibrosis resulting from chronic silicosis via limiting IL-1β and IL-18 driven inflammation. METHODS: To investigate whether tetracycline is a therapeutic option to block inflammasome-caspase-1 driven inflammation in silicosis, we incubated macrophages with silica alone or combined with tetracycline. The in vivo effect of tetracycline was determined after intratracheal administration of silica into the mouse lung. RESULTS: Tetracycline selectively blocks IL-1β production and pyroptotic cell death via inhibition of caspase-1 in macrophages exposed to silica particles. Consistent, treatment of silica-instilled mice with tetracycline significantly reduced pulmonary caspase-1 activation as well as IL-1β and IL-18 production, thereby ameliorating pulmonary inflammation and lung injury. Furthermore, prolonged tetracycline administration in a model of chronic silicosis reduced lung damage and fibrotic remodeling. CONCLUSIONS: These findings suggest that tetracycline inhibits caspase-1-dependent production of IL-1β in response to silica in vitro and in vivo. The results were consistent with tetracycline reducing silica-induced pulmonary inflammation and chronic silicosis in terms of lung injury and fibrosis. Thus, tetracycline could be effective in the treatment of patients with silicosis as well as other diseases involving silicotic inflammation.
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spelling pubmed-88228502022-02-09 Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1 Peukert, Konrad Steinhagen, Folkert Fox, Mario Feuerborn, Caroline Schulz, Susanne Seeliger, Benjamin Schuss, Patrick Schneider, Matthias Frede, Stilla Sauer, Andrea Putensen, Christian Latz, Eicke Wilhelm, Christoph Bode, Christian Respir Res Research BACKGROUND: Inhalation of dust containing silica particles is associated with severe pulmonary inflammation and lung injury leading to chronic silicosis including fibrotic remodeling of the lung. Silicosis represents a major global health problem causing more than 45.000 deaths per year. The inflammasome-caspase-1 pathway contributes to the development of silica-induced inflammation and fibrosis via IL-1β and IL-18 production. Recent studies indicate that tetracycline can be used to treat inflammatory diseases mediated by IL-1β and IL-18. Therefore, we hypothesized that tetracycline reduces silica-induced lung injury and lung fibrosis resulting from chronic silicosis via limiting IL-1β and IL-18 driven inflammation. METHODS: To investigate whether tetracycline is a therapeutic option to block inflammasome-caspase-1 driven inflammation in silicosis, we incubated macrophages with silica alone or combined with tetracycline. The in vivo effect of tetracycline was determined after intratracheal administration of silica into the mouse lung. RESULTS: Tetracycline selectively blocks IL-1β production and pyroptotic cell death via inhibition of caspase-1 in macrophages exposed to silica particles. Consistent, treatment of silica-instilled mice with tetracycline significantly reduced pulmonary caspase-1 activation as well as IL-1β and IL-18 production, thereby ameliorating pulmonary inflammation and lung injury. Furthermore, prolonged tetracycline administration in a model of chronic silicosis reduced lung damage and fibrotic remodeling. CONCLUSIONS: These findings suggest that tetracycline inhibits caspase-1-dependent production of IL-1β in response to silica in vitro and in vivo. The results were consistent with tetracycline reducing silica-induced pulmonary inflammation and chronic silicosis in terms of lung injury and fibrosis. Thus, tetracycline could be effective in the treatment of patients with silicosis as well as other diseases involving silicotic inflammation. BioMed Central 2022-02-07 2022 /pmc/articles/PMC8822850/ /pubmed/35130879 http://dx.doi.org/10.1186/s12931-022-01937-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Peukert, Konrad
Steinhagen, Folkert
Fox, Mario
Feuerborn, Caroline
Schulz, Susanne
Seeliger, Benjamin
Schuss, Patrick
Schneider, Matthias
Frede, Stilla
Sauer, Andrea
Putensen, Christian
Latz, Eicke
Wilhelm, Christoph
Bode, Christian
Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1
title Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1
title_full Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1
title_fullStr Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1
title_full_unstemmed Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1
title_short Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1
title_sort tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822850/
https://www.ncbi.nlm.nih.gov/pubmed/35130879
http://dx.doi.org/10.1186/s12931-022-01937-7
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