The major histocompatibility complex class II transactivator is differentially regulated by interferon-γ and transforming growth factor-β in microglial cells

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-γ (IFN-γ) 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-γ treatment. Transforming growth factor-β1 (TGF-β1) inhibits both type III- and IV-CIITA expression in EOC20 cells while, in EOC2 cells TGF-β1 enhances IFN-γ induced pIV-CIITA expression. Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, abrogates the TGF-β1 mediated repression of the IFN-γ 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-β1 on microglial cells.