NF-KAPPA-B AND INTERFERON REGULATORY FACTOR-1 PHYSICALLY INTERACT ANDSYNERGISTICALLY INDUCE MAJOR HISTOCOMPATIBILITY CLASS-I GENE-EXPRESSION

Major histocompatibility (MHC) class I gene expression is synergistica lly induced by the cytokines TNF-alpha and IFN-gamma. However, the mec hanism that results in synergistic activation of these genes has remai ned 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 th e adjacent interferon consensus sequence (ICS), We further demonstrate d that NF kappa B and IRF-1 physically interacted with each other and cooperatively induced MHC class I gene expression when cotransfected i nto CHP-126 neuroblastomas. These results provide a molecular mechanis m by which TNF-alpha and IFN-gamma synergistically induce the expressi on of a variety of genes involved in immune responses, including MHC c lass I.