Histone deacetylases and their role in asthma.
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.


CONCLUSIONS
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.
Allergy and Immune Disorders, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Simon G
SG
Royce
Tom C
TC
Karagiannis
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000502:physiology*; D006801:Humans; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D056572:Histone Deacetylase Inhibitors; D013267:Stilbenes; D006655:Histone Deacetylases; D000077185:Resveratrol