NFκB and Interferon Regulatory Factor 1 Physically Interact and Synergistically Induce Major Histocompatibility Class I Gene Expression

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Abstract
Major histocompatibility (MHC) class I gene expression is synergistically induced by the cytokines TNF-α and IFN-γ. However, the mechanism that results in synergistic activation of these genes has remained unclear. We demonstrated here that TNF-α induced binding of NFκB p50 and p65 to the NFκB-like element of the MHC class I promoter termed region I and IFN-γ induced binding of IRF-1 to the adjacent interferon consensus sequence (ICS). We further demonstrated that NFκB 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-α and IFN-γ synergistically induce the expression of a variety of genes involved in immune responses, including MHC class I.