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RSV infection-elicited high MMP-12–producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration
Respiratory syncytial virus (RSV) infection often exacerbates bronchial asthma, but there is no licensed RSV vaccine or specific treatments. Here we show that RSV-induced alveolar macrophages, which produce high levels of matrix metalloproteinase-12 (MMP-12), exacerbate allergic airway inflammation...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524145/ https://www.ncbi.nlm.nih.gov/pubmed/34703996 http://dx.doi.org/10.1016/j.isci.2021.103201 |
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author | Makino, Airi Shibata, Takehiko Nagayasu, Mashiro Hosoya, Ikuo Nishimura, Toshiyo Nakano, Chihiro Nagata, Kisaburo Ito, Toshihiro Takahashi, Yoshimasa Nakamura, Shigeki |
author_facet | Makino, Airi Shibata, Takehiko Nagayasu, Mashiro Hosoya, Ikuo Nishimura, Toshiyo Nakano, Chihiro Nagata, Kisaburo Ito, Toshihiro Takahashi, Yoshimasa Nakamura, Shigeki |
author_sort | Makino, Airi |
collection | PubMed |
description | Respiratory syncytial virus (RSV) infection often exacerbates bronchial asthma, but there is no licensed RSV vaccine or specific treatments. Here we show that RSV-induced alveolar macrophages, which produce high levels of matrix metalloproteinase-12 (MMP-12), exacerbate allergic airway inflammation with increased neutrophil infiltration. When mice subjected to allergic airway inflammation via exposure to the house dust mite antigen (HDM) were infected with RSV (HDM/RSV), MMP-12 expression, viral load, neutrophil infiltration, and airway hyperresponsiveness (AHR) were increased compared to those in the HDM and RSV groups. These exacerbations in the HDM/RSV group were attenuated in MMP-12-deficient mice and mice treated with MMP408, a selective MMP-12 inhibitor, but not in mice treated with dexamethasone. Finally, M2-like macrophages produced MMP-12, and its production was promoted by increase of IFN-β-induced IL-4 receptor expression with RSV infection. Thus, targeting MMP-12 represents a potentially novel therapeutic strategy for the exacerbation of asthma. |
format | Online Article Text |
id | pubmed-8524145 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-85241452021-10-25 RSV infection-elicited high MMP-12–producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration Makino, Airi Shibata, Takehiko Nagayasu, Mashiro Hosoya, Ikuo Nishimura, Toshiyo Nakano, Chihiro Nagata, Kisaburo Ito, Toshihiro Takahashi, Yoshimasa Nakamura, Shigeki iScience Article Respiratory syncytial virus (RSV) infection often exacerbates bronchial asthma, but there is no licensed RSV vaccine or specific treatments. Here we show that RSV-induced alveolar macrophages, which produce high levels of matrix metalloproteinase-12 (MMP-12), exacerbate allergic airway inflammation with increased neutrophil infiltration. When mice subjected to allergic airway inflammation via exposure to the house dust mite antigen (HDM) were infected with RSV (HDM/RSV), MMP-12 expression, viral load, neutrophil infiltration, and airway hyperresponsiveness (AHR) were increased compared to those in the HDM and RSV groups. These exacerbations in the HDM/RSV group were attenuated in MMP-12-deficient mice and mice treated with MMP408, a selective MMP-12 inhibitor, but not in mice treated with dexamethasone. Finally, M2-like macrophages produced MMP-12, and its production was promoted by increase of IFN-β-induced IL-4 receptor expression with RSV infection. Thus, targeting MMP-12 represents a potentially novel therapeutic strategy for the exacerbation of asthma. Elsevier 2021-10-02 /pmc/articles/PMC8524145/ /pubmed/34703996 http://dx.doi.org/10.1016/j.isci.2021.103201 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Makino, Airi Shibata, Takehiko Nagayasu, Mashiro Hosoya, Ikuo Nishimura, Toshiyo Nakano, Chihiro Nagata, Kisaburo Ito, Toshihiro Takahashi, Yoshimasa Nakamura, Shigeki RSV infection-elicited high MMP-12–producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration |
title | RSV infection-elicited high MMP-12–producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration |
title_full | RSV infection-elicited high MMP-12–producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration |
title_fullStr | RSV infection-elicited high MMP-12–producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration |
title_full_unstemmed | RSV infection-elicited high MMP-12–producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration |
title_short | RSV infection-elicited high MMP-12–producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration |
title_sort | rsv infection-elicited high mmp-12–producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524145/ https://www.ncbi.nlm.nih.gov/pubmed/34703996 http://dx.doi.org/10.1016/j.isci.2021.103201 |
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