Decreased Histone Deacetylase 2 (HDAC2) in Peripheral Blood Monocytes (PBMCs) of COPD Patients.
Decreased Histone Deacetylase 2 (HDAC2) in Peripheral Blood Monocytes (PBMCs) of COPD Patients.
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DOI：
10.1371/journal.pone.0147380
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Tan C;Xuan L;Cao S;Yu G;Hou Q;Wang H
组蛋白去乙酰化酶2（HDAC 2）是I类组蛋白去乙酰化酶家族成员，其在抑制慢性阻塞性肺疾病（COPD）患者气道、肺实质和肺泡巨噬细胞中的炎性基因表达中起关键作用。然而，COPD患者、吸烟者和非吸烟者外周血单核细胞（PBMC）中HDAC 2的表达、核因子κ B（NF-κB）p65和血清炎性细胞因子水平仍不清楚。PBMC获自COPD患者、健康吸烟者和健康非吸烟者。Western Blot法检测HDAC 2和NF-κB p65的表达。通过HDAC荧光免疫沉淀活性测定试剂盒评估HDAC活性。ELISA法检测血清肿瘤坏死因子-α（TNF-α）和白细胞介素-8（IL-8）水平。与吸烟者和非吸烟者相比，COPD患者PBMC中HDAC 2表达和HDAC活性降低。COPD患者NF-κB p65表达、血清TNF-α和IL-8水平均高于非吸烟者。COPD患者FEV1%pred与HDAC 2表达及HDAC活性呈正相关。与非吸烟者相比，吸烟者HDAC活性降低，NF-κB p65表达和血清TNF-α升高。HDAC 2在COPD患者PBMC中的表达降低，并与疾病严重程度相关。HDAC 2表达的减少不仅直接增强了炎症基因的表达，而且可能是NF-κB介导的炎症激活的原因。HDAC 2的降低可能作为COPD的潜在生物标志物，并预测肺功能的下降。
Histone deacetylase 2 (HDAC2) is a class I histone deacetylase family member that plays a critical role in suppressing inflammatory gene expression in the airways, lung parenchyma, and alveolar macrophages in patients with chronic obstructive pulmonary disease (COPD). However, the expression of HDAC2 in peripheral blood monocytes (PBMCs), nuclear factor kappa B (NF-κB) p65, and serum inflammatory cytokine levels in COPD patients, smokers, and non-smokers remains unclear. PBMCs were obtained from COPD patients, healthy smokers, and healthy nonsmokers. The HDAC2 and NF-κB p65 expression were quantified by Western Blot. HDAC activity was assessed by an HDAC fluorometric immunoprecipitation activity assay kit. Serum tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) levels were measured by ELISA. HDAC2 expression and HDAC activity were decreased in PBMCs in COPD patients compared with smokers and non-smokers. Increased NF-κB p65 expression, serum TNF-α and IL-8 levels were observed in COPD patients compared with nonsmokers. The FEV1%pred was positively correlated with HDAC2 expression and HDAC activity in COPD patients. Smokers had decreased HDAC activity, increased NF-κB p65 expression and serum TNF-α compared with nonsmokers. HDAC2 expression was decreased in PBMCs of COPD patients and was correlated with disease severity. The reduction of HDAC2 expression not only directly enhances the expression of inflammatory genes, but may account for the activation of NF-κB mediated inflammation. Decreased HDAC2 may serve as a potential biomarker of COPD and predict the decline of lung function.