The scavenger receptor CD163: Regulation, promoter structure and genomic organization
The scavenger receptor CD163: Regulation, promoter structure and genomic organization
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DOI：
10.1159/000028105
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发表时间：
1999-01-01
期刊：
影响因子：
5
通讯作者：
Schmitz, G
中科院分区：
文献类型：
--
作者：
Ritter, M;Buechler, C;Schmitz, G
CD163是新近发现的富含半胱氨酸的清道夫受体超家族成员，表达于外周血单核细胞和大多数组织巨噬细胞。我们证明了用重组M-CSF体外培养人血单核细胞可诱导CD163转录。相反，在GM-CSF和IL-4存在的情况下，树突状细胞分化抑制CD163mRNA和蛋白水平。鉴于CD163在炎症中的重要作用，我们研究了促炎和抗炎刺激对CD163表达的影响，发现脂多糖和干扰素-γ显著抑制CD163的表达，而IL-10或地塞米松则强烈诱导CD163的表达。地塞米松对CD163mRNA的诱导作用可能是通过位于近端启动子区域的几个糖皮质激素受体结合位点来实现的。此外，该序列还含有转录因子SP1、C/EBPα、Ets-2、PU.1和AP-I的潜在结合位点，这些转录因子在髓系特异性基因的表达中发挥着重要作用。我们还在转录起始点上游发现了一个可能影响启动子活性的L1转座元件1.4kb。CD163的功能也可能依赖于不同亚型的使用。已经描述了CD163 mRNA的几种变体，它们编码具有改变的胞浆或胞外结构域的蛋白质，因此它们的功能特性可能不同。我们分析了CD163基因的基因组组织，可以证明这些异构体是选择性剪接的结果。对这些亚型的进一步鉴定可能有助于理解CD163的完整功能。版权所有(C)2000 S.Karger AG，巴塞尔。
CD163 is a recently identified member of the scavenger receptor cysteine-rich superfamily expressed on peripheral blood monocytes and most tissue macrophages. We demonstrate that in vitro culture of human blood monocytes with recombinant M-CSF induces CD163 transcription. In contrast, dendritic differentiation in the presence of GM-CSF and IL-4 suppresses CD163 mRNA and protein levels. Because an important function of CD163 in inflammation has been suggested, we investigated the influence of pro- and anti-inflammatory stimuli on CD163 expression and found a significant suppression by lipoposaccharide and IFN-gamma, whereas IL-10 or dexamethasone strongly induced the expression of CD163. The induction of CD163 mRNA by dexamethasone is suggested to be mediated by several glucocorticoid receptor binding sites located in the proximal promoter region. In addition, this sequence contains potential binding sites for the transcription factors Spl, C/EBP alpha, Ets-2, PU.1 and AP-I, which have been shown to play an important role in myeloid-specific gene expression. We also identified an L1-transposable element 1.4 kb upstream of the transcription start site that might influence the promoter activity. The function of CD163 may also depend on the use of different isoforms. Several variants of CD163 mRNA have been described that encode proteins with altered cytoplasmic or extracellular domains and thus may differ in their functional properties. We analyzed the genom ic organization of the CD163 gene and could demonstrate that these isoforms result from alternative splicing. Further characterization of the isoforms may help to understand the complete function of CD163. Copyright (C) 2000 S. Karger AG, Basel.