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

Abstract

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.