Hsp70: A Chaperokine

Chaperokine is a term recently coined to better describe the dual role of extracellular heat shock protein as both chaperone and cytokine. The augmentation of intracellular Hsp72 expression has clearly been demonstrated to be cytoprotective; with the ability to activate anti-apoptotic and anti-inflammatory pathways, exerting inhibitory effects on cell cycle progression and suppressing genes important in proliferation and differentiation. On the other hand, the role of extracellular Hsp72 is only now being elucidated and has been demonstrated to play a cytostimulatory role by enhancing proinflammatory cytokine and chemokine synthesis, up-regulate co-stimulatory molecule expression, enhance the maturation of dendritic cells and promote antitumour surveillance. This paper covers the most recent advances in elucidation of the mechanism by which the chaperokine activity of Hsp72 is transduced, addresses its biological significance and, finally, covers how it is being harnessed to produce novel therapeutic agents.