Expression and activity of histone deacetylases in human asthmatic airways
Expression and activity of histone deacetylases in human asthmatic airways
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DOI：
10.1164/rccm.2110060
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发表时间：
2002-08-01
影响因子：
24.7
通讯作者：
Adcock, IM
中科院分区：
文献类型：
--
作者：
Ito, K;Caramori, G;Adcock, IM
哮喘是一种慢性炎症性疾病，其特征在于多种炎症基因的表达增加。染色质修饰在这些基因的调控中起着关键作用。组蛋白乙酰转移酶（HAT）引起的乙酰化与基因转录增加有关，而组蛋白去乙酰化酶（HDAC）引起的低乙酰化与基因表达抑制有关。我们检测了正常受试者和哮喘受试者支气管活检组织中HAT和HDAC的表达和活性。正常受试者和哮喘受试者之间的HDAC 1-HDAC 6表达部位没有差异，但哮喘受试者的HDAC酶活性降低，HDAC 1和HDAC 2蛋白表达降低，如Western印迹法所测。相比之下，吸入类固醇治疗的哮喘受试者的HDAC活性高于未治疗的哮喘受试者，但仍低于对照组受试者。相反，尽管HAT（CREB结合蛋白和p300/CREB结合蛋白相关因子）表达的位点没有变化，但哮喘受试者的HAT活性增加。在接受吸入性类固醇治疗的哮喘受试者中，HAT活性降低至对照水平。哮喘中HAT活性的增加和HDAC活性的降低可能是多种炎症基因表达增加的基础，而吸入性类固醇治疗至少部分逆转了这一点。
Asthma is a chronic inflammatory disease that is characterized by increased expression of multiple inflammatory genes. Chromatin modification plays a critical role in the regulation of these genes. Acetyaltion of histories by histone acetyltransferases (HATs) is associated with increased gene transcription, whereas hypocetylation induced by histone deacetylases (HDACs) is associated with suppression of gene expression. We have examined the expression and activity of HATs and HDACs in bronchial biopsies from normal subjects and subjects with asthma. There was no difference in the site of HDAC1-HDAC6 expression between normal subjects and subjects with asthma, but subjects with asthma had reduced HDAC enzymatic activity and reduced HDAC1 and HDAC2 protein expression, as measured by Western blotting. In contrast, subjects with asthma treated with inhaled steroids were found to have greater HDAC activity than untreated subjects with asthma, although still lower than control subjects. In contrast, although there was no change in the site of HAT (CREB binding protein and p300/CREB binding protein-associated factor) expression, HAT activity was increased in subjects with asthma. HAT activity was reduced to control levels in subjects with asthma treated with inhaled steroids. The increase in HAT activity and reduced HDAC activity in asthma may underlie the increased expression of multiple inflammatory genes, and this is reversed, at least in part, by treatment with inhaled steroids.