title: TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression.
abstract: Recently, a non-DNA binding protein, class II transactivator (CIITA), has been shown to be required for constitutive and IFN-gamma-inducible class II MHC transcription. The cytokine TGF-beta inhibits IFN-gamma-induced class II MHC expression at the transcriptional level. In this study, we provide evidence that TGF-beta blocks IFN-gamma-induced CIITA mRNA accumulation. TGF-beta down-regulates class II MHC and CIITA mRNA accumulation in human astroglioma and fibrosarcoma cell lines, but TGF-beta does not destabilize the CIITA message, suggesting an effect at the transcriptional level. In cells that stably overexpressed CIITA, leading to a constitutive class II MHC-positive phenotype, the inhibitory effect of TGF-beta on class II MHC was abrogated, but the cells remained responsive for expression of TGF-beta-inducible genes. Cell lines that possessed defects in TGF-beta signaling also became refractory to inhibition of IFN-gamma-induced CIITA and class II MHC expression. Our data indicate that TGF-beta suppresses IFN-gamma-induced class II MHC expression by inhibiting accumulation of CIITA mRNA.
authors.affiliation: Department of Cell Biology, University of Alabama at Birmingham, 35294, USA.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.forename: H T
authors.initials: HT
authors.lastname: Lu
authors.forename: V
authors.initials: V
authors.lastname: Nguyen
authors.forename: H
authors.initials: H
authors.lastname: Qin
authors.forename: P H
authors.initials: PH
authors.lastname: Howe
authors.forename: B A
authors.initials: BA
authors.lastname: Hocevar
authors.forename: J M
authors.initials: JM
authors.lastname: Boss
authors.forename: R M
authors.initials: RM
authors.lastname: Ransohoff
authors.forename: E N
authors.initials: EN
authors.lastname: Benveniste
mesh_terms: D001254:Astrocytoma; D005354:Fibrosarcoma; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology*; D018014:Gene Transfer Techniques; D005802:Genes, MHC Class II / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000187:drug effects; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013752:Tetracycline / Q000494:pharmacology; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D013752:Tetracycline