Histone Deacetylase Inhibitors Induce the Differentiation of Eosinophilic Leukemia EoL-1 Cells into Eosinophils

  • Ishihara Kenji (Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University) ;
  • Hong Jang-Ja (Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University) ;
  • Kaneko Motoko (Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University) ;
  • Takahashi Aki (Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University) ;
  • Sugeno Hiroki (Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University) ;
  • Kang Young-Sook (Laboratory of Pathophysiology, College of Pharmacy, Sookmyung Women's University) ;
  • Ohuchi Kazuo (Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University)
  • Published : 2006.06.01

Abstract

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 H3, inhibited the proliferation of EoL-1 cells, 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 his tones 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.

Keywords

References

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