title: Different effects of cyclic AMP and butyrate on eosinophilic differentiation, apoptosis and bcl-2 expression of a human eosinophilic leukemia cell line, EoL-1.
abstract: A human eosinophilic leukemia cell line, EoL-1, stopped proliferating at the G1 phase, differentiated into eosinophilic granule-containing cells, and died by apoptosis when stimulated with dibutyryl cyclic AMP (dbcAMP). To clarify the effects of dbcAMP, the effects of butyrate and cAMP-increasing reagents, prostaglandin E2 (PGE2) and forskolin, on EoL-1 cellular differentiation and apoptosis were examined and compared. PGE2 and forskolin but not butyrate induced differentiation to eosinophilic granule-containing cells, suggesting that cAMP played a primary role in eosinophilic differentiation of EoL-1 cells. PGE2, forskolin and butyrate, when used alone, did not induce apoptosis of EoL-1 cells significantly at the concentrations used, but sequential stimulation of EoL-1 cells with the cAMP-increasing reagents and butyrate showed that butyrate induced further maturation and apoptosis of cAMP-induced eosinophilic granule-containing cells. These results showed that cAMP and butyrate have different effects on eosinophilic differentiation and apoptosis of EoL-1 cells. The cAMP-increasing reagents and butyrate also showed different effects on expression of members of the bcl-2 family; PGE2 decreased bcl-2 and bax levels, whereas butyrate increased the bcl-2 level. PGE2 or PGE2+butyrate, but not butyrate alone, induced bcl-XS expression. EoL-1 cells constitutively expressed Fas and anti-Fas antibody induced EoL-1 cell death, but the Fas/Fas ligand system was not involved in dbcAMP-induced EoL-1 cell apoptosis. The EoL-1 cell line is thus a useful model in which to examine differentiation and apoptosis of eosinophilic leukemia cells.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Tai
authors.forename: J
authors.initials: J
authors.lastname: Eun-Young
authors.forename: H
authors.initials: H
authors.lastname: Yuji
authors.forename: K
authors.initials: K
authors.lastname: Masahiko
authors.forename: H
authors.initials: H
authors.lastname: Toshio
authors.forename: K
authors.initials: K
authors.lastname: Kenji
authors.forename: F
authors.initials: F
authors.lastname: Kenshi
authors.forename: M
authors.initials: M
authors.lastname: Mitsufumi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D003994:Bucladesine / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002454:Cell Differentiation / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004338:Drug Combinations; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D006633:Histamine Antagonists / Q000494:pharmacology*; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology
chemical_list: D002087:Butyrates; D004338:Drug Combinations; D006633:Histamine Antagonists; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D020148:Butyric Acid; D005576:Colforsin; D003994:Bucladesine; D015232:Dinoprostone