Interferon regulatory factor-2 physically interacts with NF-kappa B in vitro and inhibits NF-kappa B induction of major histocompatibility class I and beta 2-microglobulin gene expression in transfected human neuroblastoma cells.
Most neural cells constitutively lack major histocompatibility complex (MHC) class I and beta 2-microglobulin gene expression. Cytokines and viruses may, however, induce expression of these genes in some neural cells, and this correlates with factor binding to the NF-kappa B and interferon stimulated response elements of these genes. Here, we demonstrate that NF-kappa B is capable of inducing MHC class I and beta 2-microglobulin gene expression when transiently co-transfected into CHP-126 neuroblastomas, and that IRF-2 represses this induction. Interferon regulatory factor-2 (IRF-2) repression of MHC class I and beta 2-microglobulin gene expression in CHP-126 neuroblastomas may demonstrate a mechanism by which virus persists in neural cells. We show here that IRF-2 physically interacts in vitro with NF-kappa B. This interaction may contribute to the repression of the expression of these genes. Our demonstration that IRF family members, in addition to IRF-2, physically interact in vitro with NF-kappa B (p50 and p65), provides a general mechanism by which these transcription factors may, in concert, regulate the expression of a variety of genes involved in immune responses in the brain.
Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
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Drew
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Franzoso
L M
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Carlson
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Biddison
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Siebenlist
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Ozato
D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D050836:Interferon Regulatory Factor-2; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D009447:Neuroblastoma / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000276:immunology; D012097:Repressor Proteins / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000276:immunology; D001613:beta 2-Microglobulin / Q000235:genetics* / Q000276:immunology
D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; D016328:NF-kappa B; D012097:Repressor Proteins; D014157:Transcription Factors; D001613:beta 2-Microglobulin