HDACs and their inhibitors in immunology: teaching anticancer drugs new tricks.

摘要

Leoni et al. published one of the first studies demonstrating anti-inflammatory effects of HDAC inhibitors. They showed that SAHA reduced lipopolysaccharide-induced cytokine production and conca-navalin A-induced hepatoxicity in mice, as well as pro-inflammatory cytokine production in human peripheral blood mononuclear cells. Many other studies in animal models of immune-related diseases have ensued, with therapeutic effects noted in many cases although there is considerable reason for caution due to the substantial general cyto-toxicity of many HDAC inhibitors. HDAC inhibitors were also reported to exacerbate atherosclerosis and compromise host defence18 in mouse models, and loss of HDAC activity has been linked to disease exacerbation and corticosteroid insensitivity in chronic obstructive pulmonary disease.19 Such contrasting effects in different disease settings have sparked detailed investigations into immune-related functions of individual HDAC enzymes.