Gene expression alterations of human peripheral blood monocytes induced by medium-term treatment with the TH2-cytokines interleukin-4 and-13
Gene expression alterations of human peripheral blood monocytes induced by medium-term treatment with the TH2-cytokines interleukin-4 and-13
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DOI：
10.1016/j.cyto.2005.02.004
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发表时间：
2005-06-21
期刊：
影响因子：
3.8
通讯作者：
Kühn, H
中科院分区：
文献类型：
--
作者：
Chaitidis, P;O'Donnell, V;Kühn, H
TH2细胞因子IL-4和IL-13严重改变单核细胞的基因表达。我们应用基因芯片杂交、RT-PCR、免疫组织化学和活性分析等方法，量化了IL-4和IL-13对人外周血单核细胞基因表达模式的影响。在连续3天的细胞因子作用下，6种上调最强的基因产物(15-脂氧合酶-1、纤维连接蛋白、单胺氧化酶-A、CD1c、CD23A、凝血因子XIII)包括四种具有潜在抗炎活性的蛋白质：(I)15-脂氧合酶-1(290倍上调)、(Ii)纤维连接蛋白(180倍上调)、(Iii)单胺氧化酶-A(56倍上调)和(Iv)凝血因子XIII(35倍上调)。此外，其他一些与炎症消退一致的基因产物(膜联蛋白1、胶原1α2、层粘连蛋白α5、TIMP3、血红素加氧酶-1、CCL22、热休克蛋白A8)的表达也有较低程度的上调。而经典的促炎基因产物如肿瘤坏死因子α、单核细胞趋化蛋白-1、白细胞介素1、-6、-8、-18、环氧合酶-2，以及白三烯级联反应的酶和受体(5-脂氧合酶、5-脂氧合酶激活蛋白、白三烯134受体、半胱氨酰白三烯受体2)的表达显著下调。这些数据表明，用白细胞介素4/13对人外周血单核细胞进行中期治疗会改变基因表达模式，从而使细胞可能采用可分辨的表型。(C)2005爱思唯尔有限公司。保留所有权利。
The TH2-cytokines interleukins-4 and -13 severely alter gene expression of monocytic cells. We quantified the impact of interleukins-4 and -13 on the gene expression pattern of human peripheral blood monocytes applying a strategy that involved microarray hybridization, RT-PCR, immunohistochemistry and activity assays. After 3 days of continuous cytokine exposure the six most strongly upregulated gene products (15-lipoxygenase-1, fibronectin, monoamine oxidase-A, CD1c, CD23A, coagulation factor XIII) included four proteins with potential anti-inflammatory properties: (i) 15-lipoxygenase-1 (290-fold upregulation), (ii) fibronectin (180-fold upregulation), (iii) monoamine oxidase-A (56-fold upregulation) and (iv) coagulation factor XIII (35-fold upregulation). In addition, a number of other gene products, the expression of which is consistent with inflammatory resolution (annexin 1, collagen 1 alpha 2, laminin alpha 5, TIMP3, heme oxygenase-1, CCL22, heat shock protein A8), were upregulated to a lower extent. In contrast, expression of classical pro-inflammatory gene products, such as tumor necrosis factor alpha, monocyte chemotactic protein-1, interleukins-1, -6, -8, -18, cyclooxygenase-2, as well as enzymes and receptors of the leukotriene cascade (5-lipoxygenase, 5-lipoxygenase activating protein, leukotriene 134 receptor, cysteinyl leukotriene receptor 2) were significantly downregulated. These data suggest that medium-term treatment of human peripheral blood monocytes with interleukins-4/13 alters the gene expression pattern so that the cells might adopt a resolving phenotype. (c) 2005 Elsevier Ltd. All rights reserved.