The importance of the role of histone deacetylase enzymes in the pathogenesis of asthma and chronic respiratory diseases is increasingly being recognized. Similarly, the potential clinical utility of histone deacetylase enzymes in the treatment of disease is emerging. In this review, the role of histone deacetylases (HDAC) and their inhibitors in asthma and chronic obstructive pulmonary disease is discussed.
HDAC are able to catalyze the hydrolysis of acetyl groups on lysine residues of histones, causing the condensation and coiling of chromosomal DNA around histones, and therefore regulating gene expression. Histone deacetylase inhibitors act specifically or broadly on HDAC and also on nonhistone targets. Some have been used in the oncology therapeutic field for some years, but it is only more recently that they have been suggested in the treatment of asthma and other inflammatory lung diseases.
Important developments have been made in the understanding of histone deacetylase expression in normal and diseased airways and pulmonary tissue as well as effects of histone deacetylase inhibitors on structural and inflammatory cells in the lung, including cell proliferation, differentiation and apoptosis and senescence. Many of these discoveries may have implications in addressing airway inflammation, airway remodeling and airway hyperresponsiveness in asthma.
aAllergy and Immune Disorders, Murdoch Children's Research Institute
bDepartment of Pathology, The University of Melbourne, Parkville
cEpigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia
Correspondence to Dr Tom C. Karagiannis, Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, 3004, Australia. Tel: +61 3 8532 1309; fax: +61 3 8532 1100; e-mail: email@example.com