Inflammation resolution and the induction of granulocyte apoptosis by cyclin-dependent kinase inhibitor drugs

Abstract

Inflammation is a necessary dynamic tissue response to injury or infection and it's resolution is essential to return tissue homeostasis and function. Defective or dysregulated inflammation resolution contributes significantly to the pathogenesis of many, often common and challenging to treat human conditions. The transition of inflammation to resolution is an active process, involving the clearance of inflammatory cells (granulocytes), a change of mediators and their receptors, and prevention of further inflammatory cell infiltration. This review focuses on the use of cyclin dependent kinase inhibitor drugs to pharmacologically target this inflammatory resolution switch, specifically through inducing granulocyte apoptosis and phagocytic clearance of apoptotic cells (efferocytosis). The key processes and pathways required for granulocyte apoptosis, recruitment of phagocytes and mechanisms of engulfment are discussed along with the cumulating evidence for cyclin dependent kinase inhibitor drugs as pro-resolution therapeutics.