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: Miho Hayashida, Akinori Hoshika, Yuki Kanetaka, Noriko Yanase, Junichiro Mizuguchi
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 26 Issue 6 Pg. 421-9 (Jun 2006) ISSN: 1079-9907 [Print] United States
• PMID: 16734563 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Anti-Idiotypic
• Interferon-alpha
• anti-IgM
• Luciferases
• JNK Mitogen-Activated Protein Kinases

Topics

• Antibodies, Anti-Idiotypic (pharmacology)
• Apoptosis (drug effects)
• Cell Culture Techniques
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Enzyme Activation (drug effects)
• Genes, Reporter
• Humans
• Interferon-alpha (pharmacology)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Luciferases (metabolism)
• Lymphoma, B-Cell (drug therapy, metabolism)
• Membrane Potentials (drug effects)
• Mitochondria (drug effects, physiology)
• Mitochondrial Membranes (drug effects, physiology)