Mechanism for the differentiation of EoL-1 cells into eosinophils by histone deacetylase inhibitors
Mechanism for the differentiation of EoL-1 cells into eosinophils by histone deacetylase inhibitors
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DOI：
10.1159/000101401
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发表时间：
2007-01-01
影响因子：
2.8
通讯作者：
Ohuchi, Kazuo
中科院分区：
文献类型：
--
作者：
Kaneko, Motoko;Ishihara, Kenji;Ohuchi, Kazuo
背景：EoL-1细胞具有FIP1L1-PDGFRA融合基因，该基因导致嗜酸性前体细胞转化为白血病细胞。最近，我们提出HDAC抑制剂apicidin和n-丁酸盐诱导EoL-1细胞分化为嗜酸性粒细胞是由于HDAC的持续抑制。然而，apicidin 和正丁酸均不抑制 FIP1L1-PDGFRA mRNA 的表达，尽管这两种抑制剂都能抑制细胞增殖。因此，在本研究中，我们分析了参与 EoL-1 细胞增殖信号传导的 FIP1L1-PDGFR α 蛋白和磷酸化 Stat5 的水平是否会被 HDAC 抑制剂减弱。方法：EoL-1 细胞在 apicidin、TSA 或正丁酸盐存在下孵育。通过蛋白质印迹法检测FIP1L1-PDGFR α和磷酸化-Stat5。结果：用 100 nM 的 apicidin 或 500 M 的正丁酸盐处理 EoL-1 细胞可降低 FIP1L1-PDGFR α 蛋白和磷酸化-Stat5 的水平，而用 30 nM 的曲古抑菌素 A 则不会。结论：apicidin和正丁酸引起的FIP1L1-PDGFR α蛋白水平降低可能是这些HDAC抑制剂诱导EoL-1细胞分化为嗜酸性粒细胞的机制之一。版权所有 (C) 2007 S. Karger AG，巴塞尔。
Background: EoL-1 cells have a FIP1L1-PDGFRA fusion gene which causes the transformation of eosinophilic precursor cells into leukemia cells. Recently, we suggested that the induction of differentiation of EoL-1 cells into eosinophils by the HDAC inhibitors apicidin and n-butyrate is due to the continuous inhibition of HDACs. However, neither apicidin nor n-butyrate inhibited the expression of FIP1L1-PDGFRA mRNA, although both these inhibitors suppressed cell proliferation. Therefore, in this study, we analyzed whether the levels of FIP1L1-PDGFR alpha protein and phosphorylated-Stat5 involved in the signaling for the proliferation of EoL-1 cells are attenuated by HDAC inhibitors. Methods: EoL-1 cells were incubated in the presence of apicidin, TSA or n-butyrate. FIP1L1-PDGFR alpha and phosphorylated-Stat5 were detected by Western blotting. Results: Treatment of EoL-1 cells with apicidin at 100 nM or n-butyrate at 500 M decreased the levels of FIP1L1-PDGFR alpha protein and phosphorylated-Stat5, while that with trichostatin A at 30 nM did not. Conclusions: The decrease in the level of FIP1L1-PDGFR alpha protein caused by apicidin and n-butyrate might be one of the mechanisms by which EoL-1 cells are induced to differentiate into eosinophils by these HDAC inhibitors. Copyright (C) 2007 S. Karger AG, Basel.