Format

Send to

Choose Destination
Thorax. 2017 Feb;72(2):182-185. doi: 10.1136/thoraxjnl-2016-209229. Epub 2016 Oct 24.

The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome.

Author information

1
The MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
2
Department of Critical Care, Anaesthesia and Pain Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK.

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 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.

KEYWORDS:

ARDS; Innate Immunity; Neutrophil Biology

PMID:
27965411
PMCID:
PMC5284332
DOI:
10.1136/thoraxjnl-2016-209229
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center