Anacardic acid, a histone acetyltransferase inhibitor, modulates LPS-induced IL-8 expression in a human alveolar epithelial cell line A549.
Anacardic acid, a histone acetyltransferase inhibitor, modulates LPS-induced IL-8 expression in a human alveolar epithelial cell line A549.
复制标题
DOI：
10.12688/f1000research.2-78.v1
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Goto H
中科院分区：
文献类型：
--
作者：
Yasutake T;Wada H;Higaki M;Nakamura M;Honda K;Watanabe M;Ishii H;Kamiya S;Takizawa H;Goto H
目的和设计：组蛋白乙酰化过程是可逆的，受促进乙酰化的组蛋白乙酰化转移酶(HATS)和促进去乙酰化的组蛋白去乙酰化酶(HDACs)调控，组蛋白乙酰化过程被认为在许多炎症基因的调控中起关键作用。本实验采用体外培养的人肺泡上皮细胞株A549为材料，研究了脂多糖对组蛋白乙酰化的影响及其在调节白细胞介素8表达中的作用。方法：用染色质免疫沉淀(ChIP)法检测IL-8启动子区域的组蛋白H4乙酰化。用定量聚合酶链式反应和特异性免疫分析法检测IL-8的表达和产生。结果：大肠埃希菌来源的内毒素对A549细胞IL-8蛋白的产生和mRNA的表达有剂量和时间依赖性的刺激作用。芯片分析显示，脂多糖对IL-8启动子区域的组蛋白H4乙酰化有明显的促进作用。与单用内毒素相比，TSA对A549细胞IL-8的释放有剂量依赖性的刺激作用。相反，羽扇豆酸可抑制A549细胞中IL-8的产生和表达。结论：这些数据表明，通过抑制HAT改变染色质重塑，可能调节了内毒素介导的肺内促炎反应。
Objective and design: The histone acetylation processes, which are believed to play a critical role in the regulation of many inflammatory genes, are reversible and regulated by histone acetyltransferases (HATs), which promote acetylation, and histone deacetylases (HDACs), which promote deacetylation. We studied the effects of lipopolysaccharide (LPS) on histone acetylation and its role in the regulation of interleukin (IL)-8 expression. Material: A human alveolar epithelial cell line A549 was used in vitro. Methods: Histone H4 acetylation at the IL-8 promoter region was assessed by a chromatin immunoprecipitation (ChIP) assay. The expression and production of IL-8 were evaluated by quantitative polymerase chain reaction and specific immunoassay. Effects of a HDAC inhibitor, trichostatin A (TSA), and a HAT inhibitor, anacardic acid, were assessed. Results: Escherichia coli-derived LPS showed a dose- and time-dependent stimulatory effect on IL-8 protein production and mRNA expression in A549 cells in vitro. LPS showed a significant stimulatory effect on histone H4 acetylation at the IL-8 promoter region by ChIP assay. Pretreatment with TSA showed a dose-dependent stimulatory effect on IL-8 release from A549 cells as compared to LPS alone. Conversely, pretreatment with anacardic acid inhibited IL-8 production and expression in A549 cells. Conclusion: These data suggest that LPS-mediated proinflammatory responses in the lungs might be modulated via changing chromatin remodeling by HAT inhibition.