van den Bosch Thea, Kwiatkowski Marcel, Bischoff Rainer, Dekker Frank J
University of Groningen, Groningen Research Institute of Pharmacy (GRIP), Department of Chemical & Pharmaceutical Biology, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases & Tuberculosis, Hanzeplein 1, 9713 AV, Groningen, The Netherlands.
Epigenomics. 2017 Jul;9(7):1013-1028. doi: 10.2217/epi-2017-0027. Epub 2017 Jun 15.
Asthma and chronic obstructive pulmonary disease are inflammatory airway diseases for which alternative therapeutic strategies are urgently needed. Interestingly, HDAC inhibitors show anti-inflammatory effects in mouse models for these diseases. Here we explore underlying mechanisms that may explain these effects. In previous studies, effects of HDAC inhibitors on histone acetylation are often correlated with their effects on gene expression. However, effects of HDAC inhibitors on transcription factors and their acetylation status may be particularly important in explaining these effects. These effects are also cell type-specific. Recent developments (including chemoproteomics and acetylomics) allow for a more detailed understanding of the selectivity of HDAC inhibitors, which will drive their further development into applications in inflammatory airway diseases.
哮喘和慢性阻塞性肺疾病是气道炎症性疾病，迫切需要替代治疗策略。有趣的是，组蛋白去乙酰化酶（HDAC）抑制剂在这些疾病的小鼠模型中显示出抗炎作用。在此，我们探讨可能解释这些作用的潜在机制。在先前的研究中，HDAC抑制剂对组蛋白乙酰化的作用通常与其对基因表达的作用相关。然而，HDAC抑制剂对转录因子及其乙酰化状态的作用在解释这些作用时可能尤为重要。这些作用也是细胞类型特异性的。最近的进展（包括化学蛋白质组学和乙酰化蛋白质组学）使人们能够更详细地了解HDAC抑制剂的选择性，这将推动其在气道炎症性疾病中的进一步应用开发。
