SPECIFIC SUPPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I AND CLASS-II GENES IN ASTROCYTES BY BRAIN-ENRICHED GANGLIOSIDES

The effect of brain-enriched gangliosides on constitutive and cytokine-inducible expression of major histocompatibility complex (MHC) class I and II genes in cultured astrocytes was studied. Before treatment with gangliosides, astrocytes expressed constitutive MHC class I but not class II molecules, however, the expression of both MHC class I and II cell surface molecules on astrocytes was induced to high levels by interferon gamma (IFN-gamma). Constitutive and IFN-gamma-inducible expression of MHC class I and II molecules was suppressed by treatment of astrocytes with exogenous bovine brain gangliosides in a dose-dependent manner. Constitutive and induced MHC class I and II mRNA levels were also suppressed by gangliosides, indicating control through transcriptional mechanisms. This was consistent with the ability of gangliosides to suppress the binding activity of transcription factors, especially NF-kappaB-like binding activity, important for the expression of both MHC class I and II genes. These studies may be important for understanding mechanisms of central nervous system (CNS-specific regulation of major histocompatibility molecules in neuroectodermal cells and the role of gangliosides in regulating MHC-restricted antiviral and autoimmune responses within the CNS.