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The CDK inhibitor, R-roscovitine, promotes eosinophil apoptosis by down-regulation of Mcl-1 |
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| Authors: | Rodger Duffin Andrew E Leitch Tara A Sheldrake Colette Meyer Ana L Alessandri Hugh J Brady Ian Dransfield Adriano G Rossi |
| Institution: | a MRC Centre for Inflammation Research, The Queen’s Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, Scotland, UK b Section of Immunology and Infection, Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College, South Kensington, London, UK c Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil |
| 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. |
| Keywords: | Cyclin-dependent kinase Eosinophil Apoptosis R-roscovitine Inflammation Mcl-1 Mitochondria Caspase |
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