Histone Deacetylases and Their Role in Asthma

Abstract

Objective. The aim of this article is to provide an overview of the classical histone deacetylase (HDAC) enzymes and HDAC inhibitors. The discussion is focused on the potential anti-asthmatic effects of this group of compounds. Methods. Medline was used with the search terms, “asthma and HDAC,” “asthma and Trichostatin A,” “asthma and valproic acid,” “allergic airways disease and HDAC,” “allergic airways disease and Trichostatin A,” and “allergic airways disease and valproic acid.” Manuscripts from the past decade were accessed. Historical literature dating from the 1960s was accessed for the use of anti-epileptics in the treatment of asthma. Results. Preliminary clinical trials with anti-epileptic drugs including the well-known HDAC inhibitor, valproic acid, have shown long-lasting anti-asthmatic effects providing the basis for the evaluation of this class of compounds in asthma. Studies using the prototypical HDAC inhibitor, Trichostatin A, in well-established murine models of allergic airways disease have also indicated beneficial effects. Conclusion. Although the precise mechanisms are still controversial, inhibition of airway hyperresponsiveness and agonist-induced contraction as well as anti-inflammatory effects have been described for HDAC inhibitors in asthma.

• asthma
• chromatin modifications
• histone acetylatison
• histone deacetylase inhibitor
• Trichostatin A
• valproic acid

Acknowledgements

The support of the Australian Institute of Nuclear Science and Engineering is acknowledged. TCK was the recipient of AINSE awards. Epigenomic Medicine Laboratory is supported by the National Health and Medical Research Council of Australia. KV is supported by a Baker IDI postgraduate scholarship, which is supported in part by the Victorian Government’s Operational Infrastructure Support Program. The authors acknowledge the use of the facilities provided by Monash Micro Imaging at AMREP and particularly, the expert assistance from Drs Stephen Cody and Iśka Carmichael.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.