title: Modulation of major histocompatibility complex class I genes by interferon-gamma and ganglioside GT 1b in astrocytes: involvement of protein tyrosine phosphatases.
abstract: We have previously reported that the polysialoganglioside GT1b suppresses the induction of major histocompatibility complex class I molecules by interferon-gamma in astrocytes. Suppression by GT1b depended on the presence of sialic acid moieties because asialo-GM1 was not suppressive. In the present report, GT1b was found to act transcriptionally to suppress class I genes because both the interferon-gamma induction of RNA and the activity of class I promoter constructs were inhibited. Furthermore, GT1b suppressed promoter activity through interferon regulatory factor elements, indicating an effect on the transcription activation factor, interferon regulatory factor 1. Interferon-gamma induced interferon regulatory factor 1 within 8 h, and GT1b suppressed this induction. The suppression of interferon regulatory factor 1 by GT1b correlated with the suppression of gamma-activated factor binding at the promoter of the interferon regulatory factor 1 gene. The suppression of gamma-activated factor by GT1b appeared to involve increased protein tyrosine phosphatase activity because treatment of the cells with pervanadate reversed the effect of GT1b on the gamma-activated factor and, correspondingly, phosphotyrosine content. In sum, GT1b displays specific effects on interferon-gamma signaling and negative feedback regulatory molecules in astrocytes.
authors.affiliation: Department of Neurology, State University of New York, Health Science Center, Syracuse 13210, USA.
authors.forename: P T
authors.initials: PT
authors.lastname: Massa
authors.forename: C
authors.initials: C
authors.lastname: Wu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism; D005434:Flow Cytometry; D005732:Gangliosides / Q000494:pharmacology*; D005805:Genes, MHC Class I / Q000187:drug effects*; D017930:Genes, Reporter; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D005732:Gangliosides; D015395:Histocompatibility Antigens Class I; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C016481:trisialoganglioside GT1; D007371:Interferon-gamma; D015500:Chloramphenicol O-Acetyltransferase; D017027:Protein Tyrosine Phosphatases