Targeting histone deacetylase 2 in chronic obstructive pulmonary disease treatment

Publisher Website
Google Scholar
Abstract
There is increasing evidence that histone acetylation plays a critical role in the regulation of inflammatory genes and in mediating the anti-inflammatory effects of corticosteroids. Inflammatory stimuli through transcription factors, such as NF-κB, recruit co-activator molecules with intrinsic histone acetyltransferase activity, leading to hyperacetylation of core histones and gene activation. Histone deacetylases (HDACs) reverse this process and suppress inflammatory genes. Corticosteroids, the most effective anti-inflammatory drugs so far available, recruit HDAC2 to activated inflammatory gene complexes through an interaction with glucocorticoid receptor and thus switch off activated inflammatory genes. In chronic obstructive pulmonary disease and in asthmatic patients who smoke, there is a reduction in HDAC2 activity and expression, resulting in amplification of inflammation and corticosteroid resistance. Therapeutic strategies to increase HDAC activity may, therefore, be expected to reduce inflammati...

This publication has 64 references indexed in Scilit: