title: Differentiation of eosinophilic leukemia EoL-1 cells into eosinophils induced by histone deacetylase inhibitors.
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 without attenuating the level of FIP1L1-PDGFRA mRNA, and induced the expression of markers for mature eosinophils such as integrin beta7, 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.
authors.affiliation: Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi 980-8578, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishihara
authors.forename: Aki
authors.initials: A
authors.lastname: Takahashi
authors.forename: Motoko
authors.initials: M
authors.lastname: Kaneko
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sugeno
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hirasawa
authors.forename: JangJa
authors.initials: J
authors.lastname: Hong
authors.forename: OkPyo
authors.initials: O
authors.lastname: Zee
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohuchi
mesh_terms: D000107:Acetylation / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects* / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000201:enzymology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002087:Butyrates; D004791:Enzyme Inhibitors; C479818:FIP1L1 protein, human; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D010456:Peptides, Cyclic; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C102351:apicidin; D039221:mRNA Cleavage and Polyadenylation Factors; C012589:trichostatin A; D006655:Histone Deacetylases