Roscovitine blocks leukocyte extravasation by inhibition of cyclin-dependent kinases 5 and 9.

ABSTRACT:

Background and purpose

Roscovitine, a cyclin-dependent kinase (CDK) inhibitor that induces tumour cell death, is under evaluation as an anti-cancer drug. By triggering leukocyte apoptosis, roscovitine can also enhance the resolution of inflammation. Beyond death-inducing properties, we tested whether roscovitine affects leukocyte-endothelial cell interaction, a vital step in the onset of inflammation.

Experimental approach

Leukocyte-endothelial cell interactions were evaluated in venules of mouse cremaster muscle, using intravital microscopy. In primary human endothelial cells, we studied the influence of roscovitine on adhesion molecules and on the nuclear factor-κB (NF-κB) pathway. A cellular kinome array, in vitro CDK profiling and RNAi methods were used to identify targe

SUBMITTER: Berberich N 

PROVIDER: S-EPMC3130954 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature