title: Tumor necrosis factor alpha regulates expression of the major histocompatibility complex class II-associated invariant chain by binding of an NF-kappa B-like factor to a promoter element.
abstract: Expression of the major histocompatibility complex (MHC) class I and class II antigens and the class II-associated invariant chain (Ii) is strongly increased by treatment of cells with tumor necrosis factor alpha (TNF-alpha) and gamma interferon. We investigated elevation of expression of the invariant chain gene by TNF-alpha. Rat fibroblast cells transfected with the mouse Ii gene containing 802 base pairs of 5' sequences could be stimulated for Ii expression by treatment with TNF-alpha. Analysis of 5'-deleted Ii gene promoter-CAT constructs provided evidence for the presence of a TNF-alpha response box (TRB). Cloning of TRB in front of a non-TNF-alpha-responsive promoter could transfer the TNF-alpha stimulatory effect. We demonstrate binding of a TNF-alpha-induced factor to a kappa B-like motif within TRB. Mutations introduced into the kappa B element of the Ii promoter-CAT plasmid abolished the TNF-alpha-mediated stimulatory effect. Comparison of the TNF-alpha-induced factor and lipopolysaccharide-induced NF-kappa B in gel mobility shift assays upon partial protease digestion suggests similar DNA-binding protein cores. Further support for the NF-kappa B-like nature of the TNF-alpha-induced factor was obtained in methylation interference assays. The TNF-alpha-induced nuclear factor comprises DNA contact sites that are identical to those described for NF-kappa B. This TNF-alpha-induced factor also interacts with kappa B-like sequences of the MHC Kb, Ek alpha, and beta 2-microglobulin promoter, suggesting a common TNF-alpha-mediated regulatory signal for expression of MHC antigens and Ii.
authors.affiliation: Institute of Immunology and Genetics, German Cancer Research Center, Heidelberg.
authors.forename: U
authors.initials: U
authors.lastname: Pessara
authors.forename: N
authors.initials: N
authors.lastname: Koch
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005802:Genes, MHC Class II / Q000187:drug effects*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008745:Methylation; D008969:Molecular Sequence Data; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C045084:invariant chain; D015500:Chloramphenicol O-Acetyltransferase