17β-estradiol inhibits class II major histocompatibility complex (MHC) expression:: Influence on histone modifications and CBP recruitment to the class II MHC promoter
17β-estradiol inhibits class II major histocompatibility complex (MHC) expression:: Influence on histone modifications and CBP recruitment to the class II MHC promoter
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DOI：
10.1210/me.2004-0098
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发表时间：
2004-08-01
影响因子：
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通讯作者：
Benveniste, EN
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文献类型：
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作者：
Adamski, J;Ma, ZD;Benveniste, EN
主要组织相容性复合体（MHC）II类蛋白对于免疫应答的起始是重要的，并且对于免疫系统特异性识别外来抗原是必需的。II类MHC表达的调节主要发生在转录水平。II类反式激活蛋白是组成型和干扰素-γ-诱导型II类MHC表达所必需的主调节因子。雌激素[17 β-雌二醇（17 β-E-2）]已被证明具有免疫调节作用。在这项研究中，我们发现，17 β-E-2下调干扰素-γ诱导的II类MHC蛋白水平的脑内皮细胞，以及其他类型的细胞（星形胶质细胞，纤维肉瘤细胞，巨噬细胞）。17 β-E-2对II类MHC表达的抑制作用不是由于II类反式激活因子mRNA或蛋白水平的变化，而是17 β-E-2在II类MHC基因表达水平介导抑制。我们证明，17 β-E-2减弱H3和H4组蛋白乙酰化和cAMP反应元件结合蛋白结合蛋白与II类MHC启动子的关联，表明17 β-E-2通过一种新的机制抑制II类MHC表达，该机制涉及II类MHC启动子的组蛋白乙酰化状态的修饰。
Major histocompatibility complex (MHC) class II proteins are important for the initiation of immune responses and are essential for specific recognition of foreign antigens by the immune system. Regulation of class II MHC expression primarily occurs at the transcriptional level. The class II transactivator protein is the master regulator that is essential for both constitutive and interferon-gamma-inducible class II MHC expression. Estrogen [17beta-estradiol (17beta-E-2)] has been shown to have immunomodulatory effects. In this study, we show that 17beta-E-2 down-regulates interferon-gamma inducible class II MHC protein levels on brain endothelial cells, as well as other cell types (astrocytes, fibrosacroma cells, macrophages). The inhibitory effects of 17beta-E-2 on class II MHC expression are not due to changes in class II transactivator mRNA or protein levels, rather, 17beta-E-2 mediates inhibition at the level of class II MHC gene expression. We demonstrate that 17beta-E-2 attenuates H3 and H4 histone acetylation and cAMP response element binding protein-binding protein association with the class II MHC promoter, suggesting that 17beta-E-2 inhibits class II MHC expression by a novel mechanism involving modification of the histone acetylation status of the class II MHC promoter.