Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis.

Apoptosis is essential for clearance of potentially injurious inflammatory cells and subsequent efficient resolution of inflammation. Here we report that human neutrophils contain functionally active cyclin-dependent kinases (CDKs), and that structurally diverse CDK inhibitors induce caspase-dependent apoptosis and override powerful anti-apoptosis signals from survival factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF). We show that the CDK inhibitor R-roscovitine (Seliciclib or CYC202) markedly enhances resolution of established neutrophil-dependent inflammation in carrageenan-elicited acute pleurisy, bleomycin-induced lung injury, and passively induced arthritis in mice.

Regulation of neutrophil apoptosis and removal of apoptotic cells.

The accumulation of neutrophils during inflammation is essential for the destruction and removal of invading microorganisms. However, for resolution of inflammation to occur, neutrophils must also be removed from the inflammatory site since these cells are capable of releasing tissue toxic molecules. Neutrophil removal has been shown to occur via apoptosis and phagocyte clearance of apoptotic cells.

Golgi fragmentation during Fas-mediated apoptosis is associated with the rapid loss of GM130.

During apoptosis, the Golgi complex becomes fragmented and key proteins (e.g., GRASP65 and p115) are targets for caspase cleavage.

6th World Congress on Inflammation.

The 6th World Congress on Inflammation was held in the Vancouver Convention and Exhibition Center. This biennial meeting was organised by the Inflammation Research Association (USA) and Triangle 3 Ltd (UK), under the auspices of the International Association of Inflammation Societies. This meeting aimed to promote international cooperation amongst inflammation scientists and provide a communication network for various inflammation societies from around the world.