NF kappa B and interferon regulatory factor 1 physically interact and synergistically induce major histocompatibility class I gene expression.
Major histocompatibility (MHC) class I gene expression is synergistically induced by the cytokines TNF-alpha and IFN-gamma. However, the mechanism that results in synergistic activation of these genes has remained unclear. We demonstrated here that TNF-alpha induced binding of NF kappa B p50 and p65 to the NF kappa B-like element of the MHC class I promoter termed region I and IFN-gamma induced binding of IRF-1 to the adjacent interferon consensus sequence (ICS). We further demonstrated that NF kappa B and IRF-1 physically interacted with each other and cooperatively induced MHC class I gene expression when cotransfected into CHP-126 neuroblastomas. These results provide a molecular mechanism by which TNF-alpha and IFN-gamma synergistically induce the expression of a variety of genes involved in immune responses, including MHC class I.
Drew
P D
PD
Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Franzoso
G
G
Becker
K G
KG
Bours
V
V
Carlson
L M
LM
Siebenlist
U
U
Ozato
K
K
D001483:Base Sequence; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005805:Genes, MHC Class I; D005822:Genetic Vectors; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D013268:Stimulation, Chemical; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D016328:NF-kappa B; D010750:Phosphoproteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma