title: Involvement of TRAIL/TRAIL-R interaction in IFN-alpha-induced apoptosis of Daudi B lymphoma cells.
abstract: Interferon-alpha (IFN-alpha) exerts the anti-tumour effect on various tumours at least partly through induction of apoptosis. Apoptosis is induced by members of the tumour necrosis factor (TNF) family, including Fas (CD95) and TNF-related apoptosis-inducing ligand (TRAIL). In the present study, we examined whether the TRAIL/TRAIL-R system is involved in IFN-alpha-induced apoptosis using Daudi B lymphoma cells. IFN-alpha upregulated the expression of TRAIL within 12 h, as assessed by flow cytometry and RT-PCR, and the level increased with time until 72 h. The levels of both TRAIL-R1 and TRAIL-R2, low in Daudi cells, were enhanced by IFN-alpha. The enhanced TRAIL-R1/-R2 appeared to function as a death-inducing molecule since IFN-alpha-stimulated cells were more susceptible to TRAIL-induced cell death. The IFN-alpha-stimulated Daudi cells or their derived culture supernatants displayed cytotoxicity against TRAIL-sensitive, but not resistant lines. Moreover, the IFN-alpha-induced reduction in mitochondrial membrane potential preceding the induction of apoptosis was substantially prevented by neutralizing anti-TRAIL monoclonal antibody. Taken together, IFN-alpha-induced apoptosis appears to be mediated by the autocrine and/or paracrine loop involving TRAIL/TRAIL-R.
authors.affiliation: Department of Immunology and Intractable Disease, Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Oshima
authors.forename: N
authors.initials: N
authors.lastname: Yanase
authors.forename: C
authors.initials: C
authors.lastname: Ibukiyama
authors.forename: A
authors.initials: A
authors.lastname: Yamashina
authors.forename: N
authors.initials: N
authors.lastname: Kayagaki
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: J
authors.initials: J
authors.lastname: Mizuguchi
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D016923:Cell Death / Q000276:immunology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; D006131:Growth Inhibitors; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha