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The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome
Acute respiratory distress syndrome (ARDS) is a neutrophil-dominant disorder with no effective pharmacological therapies. While the cyclin-dependent kinase inhibitor AT7519 induces neutrophil apoptosis to promote inflammation resolution in preclinical models of lung inflammation, its potential effic...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5284332/ https://www.ncbi.nlm.nih.gov/pubmed/27965411 http://dx.doi.org/10.1136/thoraxjnl-2016-209229 |
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author | Dorward, David A Felton, Jennifer M Robb, Calum T Craven, Thomas Kipari, Tiina Walsh, Timothy S Haslett, Christopher Kefala, Kallirroi Rossi, Adriano G Lucas, Christopher D |
author_facet | Dorward, David A Felton, Jennifer M Robb, Calum T Craven, Thomas Kipari, Tiina Walsh, Timothy S Haslett, Christopher Kefala, Kallirroi Rossi, Adriano G Lucas, Christopher D |
author_sort | Dorward, David A |
collection | PubMed |
description | Acute respiratory distress syndrome (ARDS) is a neutrophil-dominant disorder with no effective pharmacological therapies. While the cyclin-dependent kinase inhibitor AT7519 induces neutrophil apoptosis to promote inflammation resolution in preclinical models of lung inflammation, its potential efficacy in ARDS has not been examined. Untreated peripheral blood sepsis-related ARDS neutrophils demonstrated prolonged survival after 20 hours in vitro culture. AT7519 was able to override this phenotype to induce apoptosis in ARDS neutrophils with reduced expression of the pro-survival protein Mcl-1. We demonstrate the first pharmacological compound to induce neutrophil apoptosis in sepsis-related ARDS, highlighting cyclin-dependent kinase inhibitors as potential novel therapeutic agents. |
format | Online Article Text |
id | pubmed-5284332 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-52843322017-02-07 The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome Dorward, David A Felton, Jennifer M Robb, Calum T Craven, Thomas Kipari, Tiina Walsh, Timothy S Haslett, Christopher Kefala, Kallirroi Rossi, Adriano G Lucas, Christopher D Thorax Research Letter Acute respiratory distress syndrome (ARDS) is a neutrophil-dominant disorder with no effective pharmacological therapies. While the cyclin-dependent kinase inhibitor AT7519 induces neutrophil apoptosis to promote inflammation resolution in preclinical models of lung inflammation, its potential efficacy in ARDS has not been examined. Untreated peripheral blood sepsis-related ARDS neutrophils demonstrated prolonged survival after 20 hours in vitro culture. AT7519 was able to override this phenotype to induce apoptosis in ARDS neutrophils with reduced expression of the pro-survival protein Mcl-1. We demonstrate the first pharmacological compound to induce neutrophil apoptosis in sepsis-related ARDS, highlighting cyclin-dependent kinase inhibitors as potential novel therapeutic agents. BMJ Publishing Group 2017-02 2016-10-24 /pmc/articles/PMC5284332/ /pubmed/27965411 http://dx.doi.org/10.1136/thoraxjnl-2016-209229 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Research Letter Dorward, David A Felton, Jennifer M Robb, Calum T Craven, Thomas Kipari, Tiina Walsh, Timothy S Haslett, Christopher Kefala, Kallirroi Rossi, Adriano G Lucas, Christopher D The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome |
title | The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome |
title_full | The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome |
title_fullStr | The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome |
title_full_unstemmed | The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome |
title_short | The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome |
title_sort | cyclin-dependent kinase inhibitor at7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome |
topic | Research Letter |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5284332/ https://www.ncbi.nlm.nih.gov/pubmed/27965411 http://dx.doi.org/10.1136/thoraxjnl-2016-209229 |
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