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.
Curr Opin Allergy Clin Immunol. 2014 Feb;14(1):44-8. doi: 10.1097/ACI.0000000000000029.
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.
组蛋白去乙酰化酶（HDAC）在哮喘和慢性呼吸系统疾病发病机制中的作用正越来越受到重视。同样，HDAC 酶在疾病治疗中的潜在临床应用也逐渐显现。本文讨论了 HDAC 及其抑制剂在哮喘和慢性阻塞性肺疾病中的作用。
HDAC 能够催化组蛋白赖氨酸残基上乙酰基的水解，导致染色体 DNA 围绕组蛋白凝聚和卷曲，从而调节基因表达。组蛋白去乙酰化酶抑制剂特异性或广泛地作用于 HDAC，也作用于非组蛋白靶点。一些抑制剂已在肿瘤治疗领域使用多年，但直到最近才被提议用于治疗哮喘和其他炎症性肺部疾病。
在正常和患病气道以及肺组织中 HDAC 表达的理解，以及 HDAC 抑制剂对肺内结构细胞和炎性细胞的作用方面取得了重要进展，包括细胞增殖、分化和凋亡以及衰老。这些发现中的许多可能对解决哮喘中的气道炎症、气道重塑和气道高反应性具有重要意义。
