Journal
ANNUAL REVIEW OF PHYSIOLOGY
Volume 71, Issue -, Pages 451-464Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev.physiol.010908.163257
Keywords
histone acetylation; histone deacetylase; macrophage; theophylline; oxidative stress; nuclear factor-kappa B
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Chronic obstructive pulmonary disease (COPD), characterized by progressive inflammation in the small airways and lung parenchyma, is mediated by the increased expression of multiple inflammatory genes. The increased expression of these genes is regulated by acetylation of core histones, whereas histone deacetylase 2 (HDAC2) suppresses inflammatory gene expression. In COPD, HDAC2 activity and expression are reduced in peripheral lung and in alveolar microphages, resulting in amplification of the inflammatory response. Corticosteroid resistance in COPD occurs because corticosteroids use HDAC2 to switch off activated inflammatory genes. The reduction in HDAC2 appears to be secondary to the increased oxidative and nitrative stress in COPD lungs. Antioxidants and inhibitors of nitric oxide synthesis may therefore restore corticosteroid sensitivity in COPD, but this can also be achieved by low concentrations of theophylline and curcumin, which act as HDAC activators.
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