title: Autocrine cell suicide in a Burkitt lymphoma cell line (Daudi) induced by interferon alpha: involvement of tumor necrosis factor as ligand for the CD95 receptor.
abstract: The CD95 receptor, a member of the tumor necrosis factor (TNF) receptor superfamily, mediates signals for cell death on specific ligand or antibody engagement. It was hypothesized that interferon alpha (IFN-alpha) induces apoptosis through activation of the CD95-mediated pathway and that CD95 and ligands of the death domain may belong to the group of IFN-stimulated genes. Therefore, the effect of IFN-alpha on CD95-CD95L expression, on the release of TNF-alpha, and on TNF receptor 1 expression in an IFN-sensitive human Burkitt lymphoma cell line (Daudi) was investigated. After 5 days' incubation, apoptosis in 81% of IFN-alpha-treated Daudi cells was preceded by a release of TNF-alpha and an induction of CD95 receptor expression. Although supernatants of IFN-treated Daudi cells induced apoptosis of CD95-sensitive Jurkat cells, CD95L was undetectable on protein or on messenger RNA levels, and the weak initial expression of TNF receptor 1 increased only slightly during IFN treatment. Surprisingly, binding of TNF-alpha to CD95 was observed and confirmed by 3 different techniques-enzyme-linked immunosorbent assay using immobilized CD95:Fc-immunoglobulin G, immunoprecipitation assay using CD95 receptor precipitates of Daudi cells, and binding of sodium iodide 125-TNF-alpha to Daudi cells, which was strongly stimulated by IFN-alpha and inhibited by CD95L, CD95:Fc, unlabeled TNF-alpha, and anti-TNF-alpha antibody. Preincubation of Daudi cells with antagonists of the CD95-mediated pathway resulted in an inhibition of IFN-alpha-mediated cell death. The present investigation shows that IFN-alpha induces autocrine cell suicide of Daudi cells by a cross-talk between the CD95 receptor and TNF-alpha. The CD95 receptor can be considered a third TNF receptor, in addition to p55 and p75.
authors: Departments of Internal Medicine I and Nuclear Medicine and the Ludwig Boltzmann Institut for Experimental Endocrinology, University of Vienna, Austria. heinz.gisslinger@akh-wien.ac.at
authors: H
authors: H
authors: Gisslinger
authors: R
authors: R
authors: Kurzrock
authors: B
authors: B
authors: Gisslinger
authors: S
authors: S
authors: Jiang
authors: S
authors: S
authors: Li
authors: I
authors: I
authors: Virgolini
authors: W
authors: W
authors: Woloszczuk
authors: M
authors: M
authors: Andreeff
authors: M
authors: M
authors: Talpaz
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D019898:Autocrine Communication; D016923:Cell Death / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism / Q000473:pathology*; D008024:Ligands; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D008024:Ligands; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor