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.