HDAC inhibitors TSA and sodium butyrate enhanced the human IL-5 expression by altering histone acetylation status at its promoter region
HDAC inhibitors TSA and sodium butyrate enhanced the human IL-5 expression by altering histone acetylation status at its promoter region
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HDAC 抑制剂 TSA 和丁酸钠通过改变启动子区域的组蛋白乙酰化状态来增强人 IL-5 的表达。
DOI：
10.1016/j.imlet.2006.12.001
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发表时间：
2007-02-15
影响因子：
4.4
通讯作者：
Huang, Baiqu
中科院分区：
文献类型：
--
作者：
Han, Songyan;Lu, Jun;Huang, Baiqu
IL-5的表达与嗜酸性粒细胞的成熟和分化密切相关，并且被认为是负责过敏性炎症的细胞因子。本文报道了两种HDAC特异性抑制剂曲古抑菌素A（TSA）和丁酸钠（NaBu）对HDAC活性的抑制，导致内源性和外源性IL-5启动子活性的升高。我们证明TSA和NaBu处理刺激IL-5的mRNA表达和蛋白质产生。ChIP检测结果表明TSA和NaBu处理导致Jurkat细胞中IL-5启动子上的历史H3和H4过度乙酰化，从而促进了该启动子驱动的外源荧光素酶活性。此外，定点突变研究表明，转录因子NFAT、GATA 3和YY 1在IL-5启动子上的结合位点对TSA和NaBu的作用至关重要，提示TSA和NaBu抑制剂对IL-5基因的转录激活是通过转录因子影响IL-5启动子上的HDAC功能实现的。这些数据将有助于阐明IL-5转录控制的独特机制以及与IL-5相关的过敏性疾病的治疗。(c)2006 Elsevier B. V.保留所有权利。
The expression of IL-5 correlated tightly with the maturation and differentiation of eosinophils, and is considered as a cytokine responsible for allergic inflammation. We report here that inhibition of HDAC activity by Trichostatin A (TSA) and sodium butyrate (NaBu), the two specific HDAC inhibitors, resulted in the elevation of both endogenous and exogenous activity of IL-5 promoter. We demonstrated that both the mRNA expression and protein production of IL-5 were stimulated by TSA and NaBu treatments. ChIP assays showed that treatments of TSA and NaBu caused hyperacetylation of histories H3 and H4 on IL-5 promoter in Jurkat cells, which consequently promoted the exogenous luciferase activity driven by this promoter. Moreover, site-directed mutagenesis studies showed that the binding sites for transcription factors NFAT, GATA3 and YY1 on IL-5 promoter were critical for the effects of TSA and NaBu, suggesting that the transcriptional activation of IL-5 gene by these inhibitors was achieved by affecting HDAC function on IL-5 promoter via transcription factors. These data will contribute to elucidating the unique mechanism of IL-5 transcriptional control and to the therapy of allergic disorders related to IL-5. (c) 2006 Elsevier B.V. All rights reserved.