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Phosphodiesterase 4 inhibitors attenuate virus‐induced activation of eosinophils from asthmatics without affecting virus binding
Acute respiratory virus infections, such as influenza and RSV, are predominant causes of asthma exacerbations. Eosinophils act as a double‐edged sword in exacerbations in that they are activated by viral infections but also can capture and inactivate respiratory viruses. Phosphodiesterase type 4 (PD...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245579/ https://www.ncbi.nlm.nih.gov/pubmed/32447834 http://dx.doi.org/10.1002/prp2.557 |
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author | Sabogal Piñeros, Yanaika Shari Dekker, Tamara Smids, Barbara Majoor, Christof J. Ravanetti, Lara Villetti, Gino Civelli, Maurizio Facchinetti, Fabrizio Lutter, René |
author_facet | Sabogal Piñeros, Yanaika Shari Dekker, Tamara Smids, Barbara Majoor, Christof J. Ravanetti, Lara Villetti, Gino Civelli, Maurizio Facchinetti, Fabrizio Lutter, René |
author_sort | Sabogal Piñeros, Yanaika Shari |
collection | PubMed |
description | Acute respiratory virus infections, such as influenza and RSV, are predominant causes of asthma exacerbations. Eosinophils act as a double‐edged sword in exacerbations in that they are activated by viral infections but also can capture and inactivate respiratory viruses. Phosphodiesterase type 4 (PDE4) is abundantly expressed by eosinophils and has been implicated in their activation. This exploratory study aims to determine whether these opposing roles of eosinophils activation of eosinophils upon interaction with virus can be modulated by selective PDE4 inhibitors and whether eosinophils from healthy, moderate and severe asthmatic subjects respond differently. Eosinophils were purified by negative selection from blood and subsequently exposed to RSV or influenza. Prior to exposure to virus, eosinophils were treated with vehicle or selective PDE4 inhibitors CHF6001 and GSK256066. After 18 hours of exposure, influenza, but not RSV, increased CD69 and CD63 expression by eosinophils from each group, which were inhibited by PDE4 inhibitors. ECP release, although not stimulated by virus, was also attenuated by PDE4 inhibitors. Eosinophils showed an increased Nox2 activity upon virus exposure, which was less pronounced in eosinophils derived from mild and severe asthmatics and was counteracted by PDE4 inhibitors. PDE4 inhibitors had no effect on binding of virus by eosinophils from each group. Our data indicate that PDE4 inhibitors can attenuate eosinophil activation, without affecting virus binding. By attenuating virus‐induced responses, PDE4 inhibitors may mitigate virus‐induced asthma exacerbations. |
format | Online Article Text |
id | pubmed-7245579 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72455792020-06-01 Phosphodiesterase 4 inhibitors attenuate virus‐induced activation of eosinophils from asthmatics without affecting virus binding Sabogal Piñeros, Yanaika Shari Dekker, Tamara Smids, Barbara Majoor, Christof J. Ravanetti, Lara Villetti, Gino Civelli, Maurizio Facchinetti, Fabrizio Lutter, René Pharmacol Res Perspect Original Articles Acute respiratory virus infections, such as influenza and RSV, are predominant causes of asthma exacerbations. Eosinophils act as a double‐edged sword in exacerbations in that they are activated by viral infections but also can capture and inactivate respiratory viruses. Phosphodiesterase type 4 (PDE4) is abundantly expressed by eosinophils and has been implicated in their activation. This exploratory study aims to determine whether these opposing roles of eosinophils activation of eosinophils upon interaction with virus can be modulated by selective PDE4 inhibitors and whether eosinophils from healthy, moderate and severe asthmatic subjects respond differently. Eosinophils were purified by negative selection from blood and subsequently exposed to RSV or influenza. Prior to exposure to virus, eosinophils were treated with vehicle or selective PDE4 inhibitors CHF6001 and GSK256066. After 18 hours of exposure, influenza, but not RSV, increased CD69 and CD63 expression by eosinophils from each group, which were inhibited by PDE4 inhibitors. ECP release, although not stimulated by virus, was also attenuated by PDE4 inhibitors. Eosinophils showed an increased Nox2 activity upon virus exposure, which was less pronounced in eosinophils derived from mild and severe asthmatics and was counteracted by PDE4 inhibitors. PDE4 inhibitors had no effect on binding of virus by eosinophils from each group. Our data indicate that PDE4 inhibitors can attenuate eosinophil activation, without affecting virus binding. By attenuating virus‐induced responses, PDE4 inhibitors may mitigate virus‐induced asthma exacerbations. John Wiley and Sons Inc. 2020-05-23 /pmc/articles/PMC7245579/ /pubmed/32447834 http://dx.doi.org/10.1002/prp2.557 Text en © 2019 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Sabogal Piñeros, Yanaika Shari Dekker, Tamara Smids, Barbara Majoor, Christof J. Ravanetti, Lara Villetti, Gino Civelli, Maurizio Facchinetti, Fabrizio Lutter, René Phosphodiesterase 4 inhibitors attenuate virus‐induced activation of eosinophils from asthmatics without affecting virus binding |
title | Phosphodiesterase 4 inhibitors attenuate virus‐induced activation of eosinophils from asthmatics without affecting virus binding |
title_full | Phosphodiesterase 4 inhibitors attenuate virus‐induced activation of eosinophils from asthmatics without affecting virus binding |
title_fullStr | Phosphodiesterase 4 inhibitors attenuate virus‐induced activation of eosinophils from asthmatics without affecting virus binding |
title_full_unstemmed | Phosphodiesterase 4 inhibitors attenuate virus‐induced activation of eosinophils from asthmatics without affecting virus binding |
title_short | Phosphodiesterase 4 inhibitors attenuate virus‐induced activation of eosinophils from asthmatics without affecting virus binding |
title_sort | phosphodiesterase 4 inhibitors attenuate virus‐induced activation of eosinophils from asthmatics without affecting virus binding |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245579/ https://www.ncbi.nlm.nih.gov/pubmed/32447834 http://dx.doi.org/10.1002/prp2.557 |
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