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 journalArticlepeer-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 languageEnglish
Pages (from-to)2540-6
Number of pages7
JournalFEBS Letters
Volume583
Issue number15
DOIs
Publication statusPublished - 2009

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