Cell type-specific regulation of major histocompatibility complex (MHC) class I gene expression in astrocytes, oligodendrocytes, and neurons.
Mechanisms of major histocompatibility complex (MHC) class I gene regulation in cells of the CNS have been studied in vitro. Astrocytes in primary cultures, but neither oligodendrocytes nor neurons, constitutively expressed cell surface MHC class I molecules. Interferon-gamma (IFN-gamma) treatment led to induction of MHC class I expression in astrocytes and oligodendrocytes but not in neurons. The conserved upstream sequence containing the juxtaposed nuclear factor (NF)-kappa B-like region I and IFN-response consensus sequence (ICS) constitutively enhanced MHC class I gene promoter activity in astrocytes, but not in oligodendrocytes or in neurons. Nuclear extracts from astrocytes, but not from oligodendrocytes and neurons, had a binding activity specific for the NF-kappa B-like region I sequence, indicating that constitutive expression of MHC class I genes is governed by the upstream region I enhancer and its binding factor. IFN-gamma treatment led to induction of MHC class I promoter activity in astrocytes and oligodendrocytes, but not in neurons. In accordance with this observation, a nuclear factor that binds to the ICS was induced in astrocytes and oligodendrocytes but not in neurons following IFN-gamma treatment. This study illustrates cell type-specific regulation of MHC class I genes in the CNS that correlates with the expression of DNA binding factors relevant to MHC class I gene transcription.
Massa
P T
PT
Department of Neurology, State University of New York, Syracuse 13210.
Ozato
K
K
McFarlin
D E
DE
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D005805:Genes, MHC Class I; D005813:Genes, Synthetic; D006183:H-2 Antigens / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic
D004268:DNA-Binding Proteins; D006183:H-2 Antigens; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D007371:Interferon-gamma