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Dexamethasone fails to improve bleomycin‐induced acute lung injury in mice
Acute respiratory distress syndrome (ARDS) features an exudative phase characterized by alveolar damage, lung edema and exacerbated inflammatory response. Given their anti‐inflammatory properties, the potential therapeutic effect of corticosteroids has been evaluated in ARDS clinical trials and expe...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854384/ https://www.ncbi.nlm.nih.gov/pubmed/31724341 http://dx.doi.org/10.14814/phy2.14253 |
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author | Aubin Vega, Mélissa Chupin, Cécile Pascariu, Mihai Privé, Anik Dagenais, André Berthiaume, Yves Brochiero, Emmanuelle |
author_facet | Aubin Vega, Mélissa Chupin, Cécile Pascariu, Mihai Privé, Anik Dagenais, André Berthiaume, Yves Brochiero, Emmanuelle |
author_sort | Aubin Vega, Mélissa |
collection | PubMed |
description | Acute respiratory distress syndrome (ARDS) features an exudative phase characterized by alveolar damage, lung edema and exacerbated inflammatory response. Given their anti‐inflammatory properties, the potential therapeutic effect of corticosteroids has been evaluated in ARDS clinical trials and experimental models of ALI. These studies produced contradictory results. Therefore, our aim was to investigate the effects of dexamethasone in an animal model of bleomycin‐induced acute lung injury and then to determine if the lack of response could be related to an impairment in repair ability of alveolar epithelial cells after injury. NMRI mice were challenged with bleomycin and then treated daily with dexamethasone or saline. Bronchoalveolar lavages (BAL) and lungs were collected for assessment of the inflammatory response and wet/dry ratio (lung edema) and for histological analyses. The effect of bleomycin and dexamethasone on wound repair was also evaluated in vitro on primary alveolar epithelial cell (ATII) cultures. Our data first showed that dexamethasone treatment did not reduce the weight loss or mortality rates induced by bleomycin. Although the TNF‐α level in BAL of bleomycin‐treated mice was reduced by dexamethasone, the neutrophil infiltration remained unchanged. Dexamethasone also failed to reduce lung edema and damage scores. Finally, bleomycin elicited a time‐ and dose‐dependent reduction in repair rates of ATII cell cultures. This inhibitory effect was further enhanced by dexamethasone, which also affected the expression of β3‐ and β6‐integrins, key proteins of alveolar repair. Altogether, our data indicate that the inability of dexamethasone to improve the resolution of ALI might be due to his deleterious effect on the alveolar epithelium repair. |
format | Online Article Text |
id | pubmed-6854384 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68543842019-12-16 Dexamethasone fails to improve bleomycin‐induced acute lung injury in mice Aubin Vega, Mélissa Chupin, Cécile Pascariu, Mihai Privé, Anik Dagenais, André Berthiaume, Yves Brochiero, Emmanuelle Physiol Rep Original Research Acute respiratory distress syndrome (ARDS) features an exudative phase characterized by alveolar damage, lung edema and exacerbated inflammatory response. Given their anti‐inflammatory properties, the potential therapeutic effect of corticosteroids has been evaluated in ARDS clinical trials and experimental models of ALI. These studies produced contradictory results. Therefore, our aim was to investigate the effects of dexamethasone in an animal model of bleomycin‐induced acute lung injury and then to determine if the lack of response could be related to an impairment in repair ability of alveolar epithelial cells after injury. NMRI mice were challenged with bleomycin and then treated daily with dexamethasone or saline. Bronchoalveolar lavages (BAL) and lungs were collected for assessment of the inflammatory response and wet/dry ratio (lung edema) and for histological analyses. The effect of bleomycin and dexamethasone on wound repair was also evaluated in vitro on primary alveolar epithelial cell (ATII) cultures. Our data first showed that dexamethasone treatment did not reduce the weight loss or mortality rates induced by bleomycin. Although the TNF‐α level in BAL of bleomycin‐treated mice was reduced by dexamethasone, the neutrophil infiltration remained unchanged. Dexamethasone also failed to reduce lung edema and damage scores. Finally, bleomycin elicited a time‐ and dose‐dependent reduction in repair rates of ATII cell cultures. This inhibitory effect was further enhanced by dexamethasone, which also affected the expression of β3‐ and β6‐integrins, key proteins of alveolar repair. Altogether, our data indicate that the inability of dexamethasone to improve the resolution of ALI might be due to his deleterious effect on the alveolar epithelium repair. John Wiley and Sons Inc. 2019-11-13 /pmc/articles/PMC6854384/ /pubmed/31724341 http://dx.doi.org/10.14814/phy2.14253 Text en © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Aubin Vega, Mélissa Chupin, Cécile Pascariu, Mihai Privé, Anik Dagenais, André Berthiaume, Yves Brochiero, Emmanuelle Dexamethasone fails to improve bleomycin‐induced acute lung injury in mice |
title | Dexamethasone fails to improve bleomycin‐induced acute lung injury in mice |
title_full | Dexamethasone fails to improve bleomycin‐induced acute lung injury in mice |
title_fullStr | Dexamethasone fails to improve bleomycin‐induced acute lung injury in mice |
title_full_unstemmed | Dexamethasone fails to improve bleomycin‐induced acute lung injury in mice |
title_short | Dexamethasone fails to improve bleomycin‐induced acute lung injury in mice |
title_sort | dexamethasone fails to improve bleomycin‐induced acute lung injury in mice |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854384/ https://www.ncbi.nlm.nih.gov/pubmed/31724341 http://dx.doi.org/10.14814/phy2.14253 |
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