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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Caspase Inhibitors
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Caspases / metabolism
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Cyclin-Dependent Kinases / antagonists & inhibitors*
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Cyclin-Dependent Kinases / metabolism
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Dose-Response Relationship, Drug
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Down-Regulation
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Eosinophils / drug effects*
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Eosinophils / physiology
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Eosinophils / ultrastructure
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Humans
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Membrane Potential, Mitochondrial / physiology
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Myeloid Cell Leukemia Sequence 1 Protein
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Protein Kinase Inhibitors / pharmacology*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Purines / pharmacology*
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Roscovitine
Substances
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Caspase Inhibitors
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Myeloid Cell Leukemia Sequence 1 Protein
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins c-bcl-2
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Purines
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Roscovitine
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Cyclin-Dependent Kinases
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Caspases