The CDK inhibitor, R-roscovitine, promotes eosinophil apoptosis by down-regulation of Mcl-1

Rodger Duffin; Andrew E Leitch; Tara A Sheldrake; John M Hallett; Colette Meyer; Sarah Fox; Ana L Alessandri; Morag C Martin; Hugh J Brady; Mauro M Teixeira; Ian Dransfield; Christopher Haslett; Adriano G Rossi

doi:10.1016/j.febslet.2009.07.017

The CDK inhibitor, R-roscovitine, promotes eosinophil apoptosis by down-regulation of Mcl-1

Rodger Duffin, Andrew E Leitch, Tara A Sheldrake, John M Hallett, Colette Meyer, Sarah Fox, Ana L Alessandri, Morag C Martin, Hugh J Brady, Mauro M Teixeira, Ian Dransfield, Christopher Haslett, Adriano G Rossi

Research output: Contribution to journal › Article › peer-review

Abstract

Eosinophils are major players in inflammatory allergic diseases such as asthma, hay fever and eczema. Here we show that the cyclin-dependent kinase inhibitor (CDKi) R-roscovitine efficiently and rapidly induces human eosinophil apoptosis using flow cytometric analysis of annexin-V/propidium iodide staining, morphological analysis by light microscopy, transmission electron microscopy and Western immunoblotting for caspase-3 cleavage. We further dissect these observations by demonstrating that eosinophils treated with R-roscovitine lose mitochondrial membrane potential and the key survival protein Mcl-1 is down-regulated. This novel finding of efficacious induction of eosinophil apoptosis by CDKi drugs has potential as a strategy for driving resolution of eosinophilic inflammation.

Original language	English
Pages (from-to)	2540-6
Number of pages	7
Journal	FEBS Letters
Volume	583
Issue number	15
DOIs	https://doi.org/10.1016/j.febslet.2009.07.017
Publication status	Published - 2009

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10.1016/j.febslet.2009.07.017

http://www.sciencedirect.com/science/article/pii/S0014579309005444

Induction of neutrophil apoptosis and treatment of severe lung inflammation
Rossi, A. (Principal Investigator)
MRC
1/09/07 → 29/02/12
Project: Research

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title = "The CDK inhibitor, R-roscovitine, promotes eosinophil apoptosis by down-regulation of Mcl-1",

abstract = "Eosinophils are major players in inflammatory allergic diseases such as asthma, hay fever and eczema. Here we show that the cyclin-dependent kinase inhibitor (CDKi) R-roscovitine efficiently and rapidly induces human eosinophil apoptosis using flow cytometric analysis of annexin-V/propidium iodide staining, morphological analysis by light microscopy, transmission electron microscopy and Western immunoblotting for caspase-3 cleavage. We further dissect these observations by demonstrating that eosinophils treated with R-roscovitine lose mitochondrial membrane potential and the key survival protein Mcl-1 is down-regulated. This novel finding of efficacious induction of eosinophil apoptosis by CDKi drugs has potential as a strategy for driving resolution of eosinophilic inflammation.",

author = "Rodger Duffin and Leitch, \{Andrew E\} and Sheldrake, \{Tara A\} and Hallett, \{John M\} and Colette Meyer and Sarah Fox and Alessandri, \{Ana L\} and Martin, \{Morag C\} and Brady, \{Hugh J\} and Teixeira, \{Mauro M\} and Ian Dransfield and Christopher Haslett and Rossi, \{Adriano G\}",

year = "2009",

doi = "10.1016/j.febslet.2009.07.017",

language = "English",

volume = "583",

pages = "2540--6",

journal = "FEBS Letters",

publisher = "Wiley",

number = "15",

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TY - JOUR

T1 - The CDK inhibitor, R-roscovitine, promotes eosinophil apoptosis by down-regulation of Mcl-1

AU - Duffin, Rodger

AU - Leitch, Andrew E

AU - Sheldrake, Tara A

AU - Hallett, John M

AU - Meyer, Colette

AU - Fox, Sarah

AU - Alessandri, Ana L

AU - Martin, Morag C

AU - Brady, Hugh J

AU - Teixeira, Mauro M

AU - Dransfield, Ian

AU - Haslett, Christopher

AU - Rossi, Adriano G

PY - 2009

Y1 - 2009

N2 - Eosinophils are major players in inflammatory allergic diseases such as asthma, hay fever and eczema. Here we show that the cyclin-dependent kinase inhibitor (CDKi) R-roscovitine efficiently and rapidly induces human eosinophil apoptosis using flow cytometric analysis of annexin-V/propidium iodide staining, morphological analysis by light microscopy, transmission electron microscopy and Western immunoblotting for caspase-3 cleavage. We further dissect these observations by demonstrating that eosinophils treated with R-roscovitine lose mitochondrial membrane potential and the key survival protein Mcl-1 is down-regulated. This novel finding of efficacious induction of eosinophil apoptosis by CDKi drugs has potential as a strategy for driving resolution of eosinophilic inflammation.

AB - Eosinophils are major players in inflammatory allergic diseases such as asthma, hay fever and eczema. Here we show that the cyclin-dependent kinase inhibitor (CDKi) R-roscovitine efficiently and rapidly induces human eosinophil apoptosis using flow cytometric analysis of annexin-V/propidium iodide staining, morphological analysis by light microscopy, transmission electron microscopy and Western immunoblotting for caspase-3 cleavage. We further dissect these observations by demonstrating that eosinophils treated with R-roscovitine lose mitochondrial membrane potential and the key survival protein Mcl-1 is down-regulated. This novel finding of efficacious induction of eosinophil apoptosis by CDKi drugs has potential as a strategy for driving resolution of eosinophilic inflammation.

U2 - 10.1016/j.febslet.2009.07.017

DO - 10.1016/j.febslet.2009.07.017

M3 - Article

C2 - 19616548

VL - 583

SP - 2540

EP - 2546

JO - FEBS Letters

JF - FEBS Letters

IS - 15

ER -

The CDK inhibitor, R-roscovitine, promotes eosinophil apoptosis by down-regulation of Mcl-1

Abstract

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Induction of neutrophil apoptosis and treatment of severe lung inflammation

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