title: The major histocompatibility complex class II transactivator is differentially regulated by interferon-gamma and transforming growth factor-beta in microglial cells.
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.
authors.affiliation: Department of Immunology, Laboratory of Molecular Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
authors.forename: Tamas
authors.initials: T
authors.lastname: Pazmany
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Tomasi
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D000949:Histocompatibility Antigens Class II; D006877:Hydroxamic Acids; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C012589:trichostatin A; D007371:Interferon-gamma