Differentiation of eosinophilic leukemia EoL-1 cells into eosinophils induced by histone deacetylase inhibitors
Differentiation of eosinophilic leukemia EoL-1 cells into eosinophils induced by histone deacetylase inhibitors
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DOI：
10.1016/j.lfs.2006.12.016
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发表时间：
2007-03-06
期刊：
影响因子：
6.1
通讯作者：
Ohuchi, Kazuo
中科院分区：
文献类型：
--
作者：
Ishihara, Kenji;Takahashi, Aki;Ohuchi, Kazuo
EoL-1细胞在正丁酸盐存在下分化为嗜酸性粒细胞，但其机制仍有待阐明。由于正丁酸盐可以抑制组蛋白脱乙酰酶，我们假设组蛋白脱乙酰酶的抑制诱导EoL-1细胞分化为嗜酸性粒细胞。在这项研究中，使用正丁酸和其他两个组蛋白去乙酰化酶抑制剂，apicidin和aplastatin A，我们分析了抑制组蛋白去乙酰化酶和EoL-1细胞分化为嗜酸性粒细胞之间的关系。已经证明，apicidin和n-丁酸盐诱导组蛋白H4和143的连续乙酰化，抑制EoL-1细胞的增殖而不减弱FIP 1 L1-PDGFRA mRNA的水平，并诱导成熟嗜酸性粒细胞的标记物如整合素β 7、CCR 1和CCR 3在EoL-1细胞上的表达，而阿司他丁A引起组蛋白的短暂乙酰化，但不诱导向嗜酸性粒细胞分化。这些结果表明，持续抑制EoL-1细胞中的组蛋白去乙酰化酶诱导分化为成熟的嗜酸性粒细胞。(c)2007年爱思唯尔公司All rights reserved.
EoL-1 cells differentiate into eosinophils in the presence of n-butyrate, but the mechanism has remained to be elucidated. Because n-butyrate can inhibit histone deacetylases, we hypothesized that the inhibition of histone deacetylases induces the differentiation of EoL-1 cells into eosinophils. In this study, using n-butyrate and two other histone deacetylase inhibitors, apicidin and trichostatin A, we have analyzed the relationship between the inhibition of histone deacetylases and the differentiation into eosinophils in EoL-1 cells. It was demonstrated that apicidin and n-butyrate induced a continuous acetylation of histones H4 and 143, inhibited the proliferation of EoL-1 cells without attenuating the level of FIP1L1-PDGFRA mRNA, and induced the expression of markers for mature eosinophils such as integrin beta 7, CCR1, and CCR3 on EoL-1 cells, while trichostatin A evoked a transient acetylation of histones and induced no differentiation into eosinophils. These findings suggest that the continuous inhibition of histone deacetylases in EoL-1 cells induces the differentiation into mature eosinophils. (c) 2007 Elsevier Inc. All rights reserved.