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Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation

Eosinophils are key effector cells in allergic diseases. Here we investigated Mcl-1 (an anti-apoptotic protein) in experimental allergic airway inflammation using transgenic overexpressing human Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor. Overexpression of Mcl-1 ex...

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Autores principales: Felton, Jennifer M, Dorward, David A, Cartwright, Jennifer A, Potey, Philippe MD, Robb, Calum T, Gui, Jingang, Craig, Ruth W, Schwarze, Jürgen, Haslett, Christopher, Duffin, Rodger, Dransfield, Ian, Lucas, Christopher D, Rossi, Adriano G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361019/
https://www.ncbi.nlm.nih.gov/pubmed/32303624
http://dx.doi.org/10.1136/thoraxjnl-2019-213204
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author Felton, Jennifer M
Dorward, David A
Cartwright, Jennifer A
Potey, Philippe MD
Robb, Calum T
Gui, Jingang
Craig, Ruth W
Schwarze, Jürgen
Haslett, Christopher
Duffin, Rodger
Dransfield, Ian
Lucas, Christopher D
Rossi, Adriano G
author_facet Felton, Jennifer M
Dorward, David A
Cartwright, Jennifer A
Potey, Philippe MD
Robb, Calum T
Gui, Jingang
Craig, Ruth W
Schwarze, Jürgen
Haslett, Christopher
Duffin, Rodger
Dransfield, Ian
Lucas, Christopher D
Rossi, Adriano G
author_sort Felton, Jennifer M
collection PubMed
description Eosinophils are key effector cells in allergic diseases. Here we investigated Mcl-1 (an anti-apoptotic protein) in experimental allergic airway inflammation using transgenic overexpressing human Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor. Overexpression of Mcl-1 exacerbated allergic airway inflammation, with increased bronchoalveolar lavage fluid cellularity, eosinophil numbers and total protein, and an increase in airway mucus production. Eosinophil apoptosis was suppressed by Mcl-1 overexpression, with this resistance to apoptosis attenuated by cyclin-dependent kinase inhibition which also rescued Mcl-1-exacerbated allergic airway inflammation. We propose that targeting Mcl-1 may be beneficial in treatment of allergic airway disease.
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spelling pubmed-73610192020-07-16 Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation Felton, Jennifer M Dorward, David A Cartwright, Jennifer A Potey, Philippe MD Robb, Calum T Gui, Jingang Craig, Ruth W Schwarze, Jürgen Haslett, Christopher Duffin, Rodger Dransfield, Ian Lucas, Christopher D Rossi, Adriano G Thorax Brief Communication Eosinophils are key effector cells in allergic diseases. Here we investigated Mcl-1 (an anti-apoptotic protein) in experimental allergic airway inflammation using transgenic overexpressing human Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor. Overexpression of Mcl-1 exacerbated allergic airway inflammation, with increased bronchoalveolar lavage fluid cellularity, eosinophil numbers and total protein, and an increase in airway mucus production. Eosinophil apoptosis was suppressed by Mcl-1 overexpression, with this resistance to apoptosis attenuated by cyclin-dependent kinase inhibition which also rescued Mcl-1-exacerbated allergic airway inflammation. We propose that targeting Mcl-1 may be beneficial in treatment of allergic airway disease. BMJ Publishing Group 2020-07 2020-04-17 /pmc/articles/PMC7361019/ /pubmed/32303624 http://dx.doi.org/10.1136/thoraxjnl-2019-213204 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
spellingShingle Brief Communication
Felton, Jennifer M
Dorward, David A
Cartwright, Jennifer A
Potey, Philippe MD
Robb, Calum T
Gui, Jingang
Craig, Ruth W
Schwarze, Jürgen
Haslett, Christopher
Duffin, Rodger
Dransfield, Ian
Lucas, Christopher D
Rossi, Adriano G
Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation
title Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation
title_full Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation
title_fullStr Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation
title_full_unstemmed Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation
title_short Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation
title_sort mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361019/
https://www.ncbi.nlm.nih.gov/pubmed/32303624
http://dx.doi.org/10.1136/thoraxjnl-2019-213204
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