Epigenetic contribution to individual variation in response to lipopolysaccharide in bovine dermal fibroblasts.
Epigenetic contribution to individual variation in response to lipopolysaccharide in bovine dermal fibroblasts.
复制标题
DOI：
10.1016/j.vetimm.2013.10.015
复制
发表时间：
2014-01-15
影响因子：
1.8
通讯作者：
Kerr, David E.
中科院分区：
文献类型：
--
作者：
Green, Benjamin B.;Kerr, David E.
先天免疫信号通路在疾病相关病原体的识别和早期反应中起着至关重要的作用。遗传分析还不能完全解释先天免疫反应强度的个体差异。本研究的目的是确定表观遗传标记（DNA甲基化或组蛋白乙酰化）在控制与脂多糖（LPS）反应相关的牛基因表达中的作用。为了确定表观遗传学在控制先天免疫方面可能产生的影响，将15头奶牛的皮肤成纤维细胞暴露于5-aza-2 ' -脱氧西汀（AZA）和曲古斯汀a （TSA）中，这些奶牛先前对LPS表现出不同的反应；分别是去甲基化剂和超乙酰化剂。通过成纤维细胞IL-8蛋白产量测量，AZA-TSA暴露导致个体对LPS反应的可变性丧失。利用微阵列转录组学分析阐明表观遗传学在lps暴露后2、4和8小时先天免疫信号传导中的作用。由于AZA-TSA的单独作用，一些基因的表达发生了改变，这表明表观遗传调控元件在正常条件下改变了表达。在LPS暴露后的至少一个测量时间内，与对照培养相比，AZA-TSA处理还导致其他基因中IL-8（7.0倍），IL-6（2.5倍），TNF-α（1.6倍）和血清淀粉样蛋白a3 (SAA3)（11.3倍）的表达增加。这些数据支持表观遗传调控显著改变lps诱导的应答和组成细胞因子基因表达的结论。
The innate immune signaling pathway plays a crucial role in the recognition and early response to pathogens associated with disease. Genetic analysis has been unable to completely account for individual variability in the strength of the innate immune response. The aim of this study was to determine the role of the epigenetic markers (DNA methylation or histone acetylation) in controlling bovine gene expression in relation to the response to lipopolysaccharide (LPS). To determine the impact epigenetics may have in controlling innate immunity, dermal fibroblasts from fifteen dairy heifers having previously displayed a differential response to LPS were exposed to 5-aza-2’-deoxyctidine (AZA) and trichostatin A (TSA); de-methylating and hyper-acetylating agents, respectively. The AZA-TSA exposure resulted in a loss of variability between individuals’ response to LPS as measured by fibroblast IL-8 protein production. Transcriptomic analysis by microarray was used to elucidate the role of epigenetics in innate immune signaling at 2, 4, and 8 hours post-LPS exposure. A subset of genes displayed altered expression due to AZA-TSA alone, suggesting an epigenetic regulatory element modifying expression under normal conditions. Treatment with AZA-TSA also led to increased expression of IL-8 (7.0 fold), IL-6 (2.5 fold), TNF-α (1.6 fold), and serum amyloid A 3 (SAA3) (11.3 fold) among other genes compared to control cultures for at least one of the measured times following LPS exposure. This data supports the conclusion that epigenetic regulation significantly alters LPS-induced responses and constitutive cytokine gene expression.
登录
查看更多内容
影响因子：
4.4
作者：
Andersen, Leif Percival
通讯作者：
Andersen, Leif Percival
影响因子：
3.8
作者：
Bougarn, Salim;Cunha, Patricia;Rainard, Pascal
通讯作者：
Rainard, Pascal
影响因子：
5.5
作者：
Beutler, B;Hoebe, K;Ulevitch, RJ
通讯作者：
Ulevitch, RJ
影响因子：
3.5
作者：
Kandasamy, S.;Kerr, D. E.
通讯作者：
Kerr, D. E.
影响因子：
3.5
作者：
Dal Zotto, R.;De Marchi, M.;Bittante, G.
通讯作者：
Bittante, G.