Pazmany Tamas, Tomasi Thomas B
Department of Immunology, Laboratory of Molecular Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
J Neuroimmunol. 2006 Mar;172(1-2):18-26. doi: 10.1016/j.jneuroim.2005.10.009. Epub 2005 Dec 20.
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.
我们评估了主要组织相容性复合体II类（MHC II）反式激活因子（CIITA）基因在两种小胶质细胞系EOC2和EOC20中的表达调控。我们证明，干扰素-γ（IFN-γ）可激活EOC20中的III型和IV型CIITA mRNA以及高水平的MHC II。然而，在EOC2细胞中，IFN-γ处理后仅可检测到低水平的IV型CIITA mRNA和MHC II。转化生长因子-β1（TGF-β1）抑制EOC20细胞中III型和IV型CIITA的表达，而在EOC2细胞中，TGF-β1增强IFN-γ诱导的pIV-CIITA表达。曲古抑菌素A（TSA），一种组蛋白脱乙酰酶（HDAC）抑制剂，可消除EOC20中TGF-β1介导的对IFN-γ诱导的CIITA的抑制作用。有证据表明，TG相互作用因子（TGIF），一种已知可募集HDAC的共抑制因子，在决定TGF-β1对小胶质细胞的作用中发挥作用。
