The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome.
Thorax
; 72(2): 182-185, 2017 02.
Article
em En
| MEDLINE
| ID: mdl-27965411
ABSTRACT
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 20â
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Pirazóis
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Síndrome do Desconforto Respiratório
/
Apoptose
/
Sepse
/
Neutrófilos
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article