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Matrix Metalloproteinase-9-Dependent Release of IL-1β by Human Eosinophils
Asthma is often associated with airway eosinophilia, and therapies targeting eosinophils are now available to treat severe eosinophilic asthma. Eosinophilic asthma is often due to a type-2 immune response and production of IL-5, which leads to eosinophilopiesis and recruitment of mature eosinophils...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398033/ https://www.ncbi.nlm.nih.gov/pubmed/30906226 http://dx.doi.org/10.1155/2019/7479107 |
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author | Esnault, Stephane Kelly, Elizabeth A. Johnson, Sean H. DeLain, Larissa P. Haedt, Madeline J. Noll, Andrea L. Sandbo, Nathan Jarjour, Nizar N. |
author_facet | Esnault, Stephane Kelly, Elizabeth A. Johnson, Sean H. DeLain, Larissa P. Haedt, Madeline J. Noll, Andrea L. Sandbo, Nathan Jarjour, Nizar N. |
author_sort | Esnault, Stephane |
collection | PubMed |
description | Asthma is often associated with airway eosinophilia, and therapies targeting eosinophils are now available to treat severe eosinophilic asthma. Eosinophilic asthma is often due to a type-2 immune response and production of IL-5, which leads to eosinophilopiesis and recruitment of mature eosinophils in the airways. A concomitant type-2 and type-17 response has been reported in some individuals. IL-17 may be enhanced by IL-1β production and can lead to neutrophilic inflammation. In fact, both eosinophilic and neutrophilic (mixed granulocytic) inflammation are simultaneously present in a large population of patients with asthma. In monocyte/macrophage cell populations, release of mature IL-1β occurs via toll-like receptor ligand-induced activation of the inflammasome. Within the inflammasome, a cascade of events leads to the activation of caspase-1, which cleaves pro-IL-1β protein into a mature, releasable, and active form. We have demonstrated that eosinophils can release IL-1β in a Toll-like receptor ligand-independent fashion. The objective of this study was to determine the mechanisms underlying the production and maturation of IL-1β in cytokine-activated eosinophils. Using eosinophils from circulating blood and from bronchoalveolar lavage fluid after an airway allergen challenge, the present study demonstrates that cytokine-activated eosinophils express and release a bioactive form of IL-1β with an apparent size less than the typical 17 kDa mature form produced by macrophages. Using a zymography approach and pharmacological inhibitors, we identified matrix metalloproteinase-9 (MMP-9) as a protease that cleaves pro-IL-1β into a ~15 kDa form and allows the release of IL-1β from cytokine-activated eosinophils. Therefore, we conclude that activated eosinophils produce MMP-9, which causes the release of IL-1β in an inflammasome/caspase-1-independent manner. The production of IL-1β by eosinophils may be a link between the eosinophilic/type-2 immune response and the neutrophilic/type-17 immune response that is often associated with a more severe and treatment-refractory type of asthma. |
format | Online Article Text |
id | pubmed-6398033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-63980332019-03-24 Matrix Metalloproteinase-9-Dependent Release of IL-1β by Human Eosinophils Esnault, Stephane Kelly, Elizabeth A. Johnson, Sean H. DeLain, Larissa P. Haedt, Madeline J. Noll, Andrea L. Sandbo, Nathan Jarjour, Nizar N. Mediators Inflamm Research Article Asthma is often associated with airway eosinophilia, and therapies targeting eosinophils are now available to treat severe eosinophilic asthma. Eosinophilic asthma is often due to a type-2 immune response and production of IL-5, which leads to eosinophilopiesis and recruitment of mature eosinophils in the airways. A concomitant type-2 and type-17 response has been reported in some individuals. IL-17 may be enhanced by IL-1β production and can lead to neutrophilic inflammation. In fact, both eosinophilic and neutrophilic (mixed granulocytic) inflammation are simultaneously present in a large population of patients with asthma. In monocyte/macrophage cell populations, release of mature IL-1β occurs via toll-like receptor ligand-induced activation of the inflammasome. Within the inflammasome, a cascade of events leads to the activation of caspase-1, which cleaves pro-IL-1β protein into a mature, releasable, and active form. We have demonstrated that eosinophils can release IL-1β in a Toll-like receptor ligand-independent fashion. The objective of this study was to determine the mechanisms underlying the production and maturation of IL-1β in cytokine-activated eosinophils. Using eosinophils from circulating blood and from bronchoalveolar lavage fluid after an airway allergen challenge, the present study demonstrates that cytokine-activated eosinophils express and release a bioactive form of IL-1β with an apparent size less than the typical 17 kDa mature form produced by macrophages. Using a zymography approach and pharmacological inhibitors, we identified matrix metalloproteinase-9 (MMP-9) as a protease that cleaves pro-IL-1β into a ~15 kDa form and allows the release of IL-1β from cytokine-activated eosinophils. Therefore, we conclude that activated eosinophils produce MMP-9, which causes the release of IL-1β in an inflammasome/caspase-1-independent manner. The production of IL-1β by eosinophils may be a link between the eosinophilic/type-2 immune response and the neutrophilic/type-17 immune response that is often associated with a more severe and treatment-refractory type of asthma. Hindawi 2019-02-17 /pmc/articles/PMC6398033/ /pubmed/30906226 http://dx.doi.org/10.1155/2019/7479107 Text en Copyright © 2019 Stephane Esnault et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Esnault, Stephane Kelly, Elizabeth A. Johnson, Sean H. DeLain, Larissa P. Haedt, Madeline J. Noll, Andrea L. Sandbo, Nathan Jarjour, Nizar N. Matrix Metalloproteinase-9-Dependent Release of IL-1β by Human Eosinophils |
title | Matrix Metalloproteinase-9-Dependent Release of IL-1β by Human Eosinophils |
title_full | Matrix Metalloproteinase-9-Dependent Release of IL-1β by Human Eosinophils |
title_fullStr | Matrix Metalloproteinase-9-Dependent Release of IL-1β by Human Eosinophils |
title_full_unstemmed | Matrix Metalloproteinase-9-Dependent Release of IL-1β by Human Eosinophils |
title_short | Matrix Metalloproteinase-9-Dependent Release of IL-1β by Human Eosinophils |
title_sort | matrix metalloproteinase-9-dependent release of il-1β by human eosinophils |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398033/ https://www.ncbi.nlm.nih.gov/pubmed/30906226 http://dx.doi.org/10.1155/2019/7479107 |
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