title: IFN-alpha sensitizes daudi B lymphoma cells to anti-IgM induced loss of mitochondrial membrane potential through activation of c-Jun NH(2)-terminal kinase.
abstract: Interferon-alpha (IFN-alpha) regulates multiple biologic functions, including antiviral activity, immune regulation, cell differentiation, and cell survival or death, in a variety of cell types. We and others have recently demonstrated that IFN-alpha induces cell death through activation of c-Jun NH(2)-terminal kinase (JNK) in human Daudi B lymphoma and U266 myeloma cells. Moreover, the IFN-alpha-induced signaling pathway has been shown to cross talk with the antigen receptor-mediated signaling cascade. In the present study, we examined whether IFN-alpha affects cell death after engagement of membrane immunoglobulin (mIg) using anti-IgM. Daudi cells pretreated with low concentrations of IFN-alpha (25 or 250 U/mL) for 24 h were stimulated with anti-IgM (1-10 microg/mL) for 24 h. The cells were assayed for JNK activation, mitochondrial membrane potential (DeltaPsim) by Western blotting, and DiOC(6) staining, respectively. The IFN-alpha-primed Daudi cells showed an increased sensitivity to subsequent stimulation with anti-IgM, as assessed by JNK activation and DeltaPsim. Moreover, Daudi cells overexpressing the constitutively active or dominant-negative form of JNK were substantially susceptible or resistant to anti-IgM-induced DeltaPsim, respectively, compared with cells overexpressing the control vector alone. Taken together, these results indicate that IFN-alpha renders Daudi B lymphoma cells susceptible to anti-IgM-induced apoptosis, probably through upregulation of JNK activation.
authors.affiliation: Department of Immunology and Intractable Immune System Disease Research Center, Tokyo Medical University, Tokyo 160-8402, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Hayashida
authors.forename: Akinori
authors.initials: A
authors.lastname: Hoshika
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kanetaka
authors.forename: Noriko
authors.initials: N
authors.lastname: Yanase
authors.forename: Junichiro
authors.initials: J
authors.lastname: Mizuguchi
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004789:Enzyme Activation / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D016898:Interferon-alpha; C044203:anti-IgM; D008156:Luciferases; D048031:JNK Mitogen-Activated Protein Kinases