title: Interferon-gamma induces Ice gene expression and enhances cellular susceptibility to apoptosis in the U937 leukemia cell line.
abstract: The roles of interferons (IFNs) in apoptosis are not fully understood. In this study we show that in the U937 monoblastic leukemia cell line, pretreatment with IFN-gamma enhanced sensitivity to apoptosis triggered by gamma-irradiation or antitumor agents (etoposide or adriamycin), as well as by anti-Fas antibody. In addition, IFN-gamma caused an increased expression of the interleukin-1 beta-converting enzyme (Ice) gene, following strong induction of the interferon regulatory factor-1 (IRF-1) gene, the product of which is a transcriptional activator of the Ice gene. An inhibitor of ICE/Ced-3 family proteases, Z-Asp-CH2-DCB, blocked apoptosis in control cells as well as in IFN-gamma-pretreated cells. These results suggest that enhanced susceptibility of IFN-gamma-pretreated cells to apoptosis is mediated through the induction of Ice by IRF-1. This pathway is not affected by interleukin-1 beta (IL-1 beta) since neutralizing antibody against IL-1 beta failed to suppress the IFN-gamma-mediated enhancement of cell death, and IL-1 beta itself did not mimic the effect of IFN-gamma.
authors.affiliation: First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: S
authors.initials: S
authors.lastname: Ueda
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Matsuzaki
authors.forename: H
authors.initials: H
authors.lastname: Mohri
authors.forename: T
authors.initials: T
authors.lastname: Okubo
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D020170:Caspase 1; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004317:Doxorubicin / Q000494:pharmacology; D004790:Enzyme Induction; D005047:Etoposide / Q000494:pharmacology; D005720:Gamma Rays; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology*; D010750:Phosphoproteins / Q000096:biosynthesis; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology
chemical_list: D000903:Antibiotics, Antineoplastic; D000906:Antibodies; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D019014:fas Receptor; D005047:Etoposide; D004317:Doxorubicin; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; D020170:Caspase 1