HDAC inhibitors as anti-inflammatory agents.

ABSTRACT

Diverse cellular functions including the regulation of inflammatory gene expression, DNA repair and cell proliferation are regulated by changes in the acetylation status of histones and non-histone proteins. Many human diseases, particularly cancer, have been associated with altered patterns of histone acetylation. Furthermore, abnormal expression and activation of histone acetyltransferases, which act as transcriptional co-activators, has been reported in inflammatory diseases. Histone deacetylase (HDAC) inhibitors have been developed clinically for malignancies due to their effects on apoptosis. More recently, in vitro and in vivo data indicates that HDAC inhibitors may be anti-inflammatory due to their effects on cell death acting through acetylation of non-histone proteins. Although there are concerns over the long-term safety of these agents, they may prove useful particularly in situations where current anti-inflammatory therapies are suboptimal.