Doherty R, O'Farrelly C, Meade K G
Animal & Bioscience Research Department, Animal & Grassland Research and Innovation Centre, Teagasc, Grange, Co, Meath, Ireland.
Vet Immunol Immunopathol. 2013 Aug 15;154(3-4):102-10. doi: 10.1016/j.vetimm.2013.05.004. Epub 2013 May 10.
Epigenetic regulation of gene expression could help explain variation in responses to infection and differences in disease susceptibility in cattle. The aim of this study was to examine epigenetic mechanisms in the regulation of LPS-induced innate immune gene expression in peripheral blood mononuclear cells (PBMCs) from five healthy calves. Firstly, epigenetic enzyme gene expression (histone deacetylase (HDAC) and DNA methyltransferase (DNMT)) was measured after LPS stimulation. Secondly, the effect of the histone deacetylase inhibitor Trichostatin A (TSA) on histone H3 acetylation and on innate immune gene expression was also measured. Results showed differential expression of HDAC6, HDAC7 and DNMT3A genes in response to LPS in cells from all animals, while TSA significantly inhibited pro-inflammatory cytokine (TNF, IL2 and IFNG) expression (P<0.05), presumably by histone acetylation. These results suggest an important role for the HDAC family of enzymes in the regulation of bovine innate immune gene expression.
基因表达的表观遗传调控有助于解释牛对感染反应的差异以及疾病易感性的不同。本研究的目的是检测来自五头健康犊牛的外周血单核细胞（PBMCs）中脂多糖（LPS）诱导的先天免疫基因表达调控中的表观遗传机制。首先，在LPS刺激后检测表观遗传酶基因表达（组蛋白去乙酰化酶（HDAC）和DNA甲基转移酶（DNMT））。其次，还检测了组蛋白去乙酰化酶抑制剂曲古抑菌素A（TSA）对组蛋白H3乙酰化和先天免疫基因表达的影响。结果显示，所有动物细胞中HDAC6、HDAC7和DNMT3A基因对LPS的反应存在差异表达，而TSA显著抑制促炎细胞因子（TNF、IL2和IFNG）的表达（P<0.05），推测是通过组蛋白乙酰化实现的。这些结果表明HDAC酶家族在牛先天免疫基因表达调控中起重要作用。
