IFNα/β Promotes Cell Survival by Activating NF-κB

• Published in: Proceedings of the National Academy of Sciences - PNAS 2000-12, Vol.97 (25), p.13631-13636
• Main Authors: Yang, Chuan He, Murti, Aruna, Pfeffer, Susan R., Basu, Leela, Kim, Jong G., Pfeffer, Lawrence M.
• Format: Article
• Language: English
• Subjects: Apoptosis; B lymphocytes; Biological Sciences; Cell lines; Cell nucleus; COS cells; Epithelial cells; Hep G2 cells; Hepatocytes; interferon receptors; Receptors; Vero cells
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.250477397

IFNs play critical roles in host defense by modulating the expression of various genes via signal transducer and activator of transcription factors. We show that IFNα/β activates another important transcription factor, NF-κB. DNA-binding activity of NF-κB was induced by multiple type 1 IFNs and was promoted by IFN in a diverse group of human, monkey, rat, and murine cells. Human IFN promoted NF-κB activation in murine cells that express the human IFNα/β receptor-1 signal-transducing chain of the type 1 IFN receptor. IFN promotes inhibitor of kappa B α (IκBα) serine phosphorylation and degradation, and stimulates NF-κB DNA-binding and transcriptional activity. Importantly, IFN promotes cell survival by protecting cells against a variety of proapoptotic stimuli, such as virus infection and antibody-mediated crosslinking. Expression of superrepressor forms of IκBα, besides inhibiting IFN-mediated NF-κB activation and IκBα degradation, also enhanced apoptotic cell death in IFN-treated cells. We conclude that NF-κB activation by IFNα/β is integrated into a signaling pathway through the IFNα/β receptor-1 chain of the type 1 IFN receptor that promotes cell survival in apposition to various apoptotic stimuli.