哮喘联盟

   摘要
   综述目的：组蛋白去乙酰酶在哮喘及呼吸系统疾病发病机制中的重要作用逐渐被认可。同样的，组蛋白去乙酰酶在疾病治疗的潜在临床效用也逐渐显现。本综述讨论了组蛋白去乙酰基酶(HDAC)及其抑制剂在治疗哮喘和慢性阻塞性肺疾病的作用。
   最新研究成果：HDAC能够催化组蛋白的赖氨酸残基上的乙酰基团水解，导致组蛋白周围染色体DNA的缩合和螺旋化，从而调节基因表达。组蛋白去乙酰酶抑制剂特异性或广泛作用于HDAC和非组蛋白靶点。其中一些制剂已在肿瘤治疗领域应用数年，但在哮喘和其他炎性肺疾病治疗领域的应用仅仅最近才被提出。
   小结:对于在正常和病变的气道及肺组织中组蛋白去乙酰酶表达的认识，以及组蛋白去乙酰酶抑制剂对肺结构和炎症细胞影响（包括细胞增殖、分化和细胞衰老与凋亡）的研究已经有了重要的进展。许多这些发现对解决哮喘的气道炎症，气道重塑以及气道高反应性有着一定的启示。
 

（林江涛 审校）
Curr Opin Allergy Clin Immunol. 2013 Dec 5. [Epub ahead of print]

Histone deacetylases and their inhibitors: new implications for asthma and chronic respiratory conditions.
 

Royce SG, Karagiannis TC.
 

ABSTRACT
PURPOSE OF REVIEW: 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.
RECENT FINDINGS: 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.
SUMMARY: 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.
 

Curr Opin Allergy Clin Immunol. 2013 Dec 5. [Epub ahead of print]