Abstract
We evaluated the regulation of the major histocompatibility complex class II (MHC II) transactivator (CIITA) gene expression in two microglial cell lines, EOC2 and EOC20. We demonstrate that interferon-gamma (IFN-gamma) activates type III- and IV-CIITA mRNA and high levels of MHC II in EOC20. However, in EOC2 cells only low levels of type IV-CIITA mRNA and MHC II are detectable following IFN-gamma treatment. Transforming growth factor-beta1 (TGF-beta1) inhibits both type III- and IV-CIITA expression in EOC20 cells while, in EOC2 cells TGF-beta1 enhances IFN-gamma induced pIV-CIITA expression. Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, abrogates the TGF-beta1 mediated repression of the IFN-gamma induced CIITA in EOC20. Evidence is presented that the TG-interacting factor (TGIF), a co-repressor known to recruit HDACs, plays a role in determining the effects of TGF-beta1 on microglial cells.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Blotting, Western / methods
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Cell Differentiation / drug effects
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Cell Line
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cytosol / drug effects
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Cytosol / metabolism
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Dose-Response Relationship, Drug
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Drug Interactions
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Gene Expression / drug effects
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Gene Expression Regulation / drug effects*
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / metabolism*
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Hydroxamic Acids / pharmacology
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Interferon-gamma / pharmacology*
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Mice
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Microglia / cytology
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Microglia / drug effects*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Protein Synthesis Inhibitors / pharmacology
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RNA, Messenger / biosynthesis
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Reverse Transcriptase Polymerase Chain Reaction / methods
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STAT Transcription Factors / metabolism
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Signal Transduction / drug effects
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Time Factors
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transforming Growth Factor beta / pharmacology*
Substances
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Histocompatibility Antigens Class II
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Hydroxamic Acids
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MHC class II transactivator protein
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Nuclear Proteins
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Protein Synthesis Inhibitors
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RNA, Messenger
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STAT Transcription Factors
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Trans-Activators
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Transforming Growth Factor beta
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trichostatin A
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Interferon-gamma