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首页> 外文期刊>Molecular and Cellular Biology >Transcriptional inhibition of the interleukin-8 gene by interferon is mediated by the NF-kappa B site.
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Transcriptional inhibition of the interleukin-8 gene by interferon is mediated by the NF-kappa B site.

机译：干扰素对白介素8基因的转录抑制作用是由NF-κB位点介导的。

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The cytokine interleukin-8 (IL-8) is an important mediator of neutrophil, lymphocyte, and basophil chemotaxis and activation. Earlier we demonstrated that beta interferon (IFN-beta) can inhibit tumor necrosis factor (TNF)-induced IL-8 gene expression at the transcriptional level, apparently by a novel mechanism. To define the cis-acting elements and trans-acting factors involved in this inhibition, DNA constructs containing portions of the 5'-flanking region of the IL-8 gene were linked to the chloramphenicol acetyltransferase (CAT) reporter gene and transfected into human diploid FS-4 fibroblasts. The region spanning positions -98 to +44 was sufficient to confer both inducibility by TNF and inhibition by simultaneous treatment with IFN-beta. Inhibition of TNF- or IL-1-induced CAT activity by IFN-beta or IFN-alpha was also observed when a DNA fragment containing only the NF-IL-6 and NF-kappa B sites (positions -94 to -70) was placed upstream of the homologous or a heterologous minimal promoter. A construct containing three copies of the NF-kappa B element in front of the CAT gene also was inducible by TNF, and this stimulatory effect too was inhibited by IFN-beta, indicating that the NF-kappa B element is sufficient to confer inhibition by IFN-beta. This inhibitory effect was specific for the NF-kappa B site of the IL-8 gene since it was less marked with constructs containing three copies of the NF-kappa B site from the HLA-B7 gene. Gel shift assays with a probe containing the NF-kappa B and NF-IL-6 binding sites of the IL-8 gene (positions -101 to -63) showed that IFN-beta treatment did not block the activation of NF-kappa B proteins or their ability to bind to the NF-kappa B site. However, nuclear extracts from cells treated with TNF in the presence of IFN-beta gave rise to an additional band that appears to contain protein components from the NF-kappa B and NF-IL-6 families. NF-kappa B site-mediated suppression of IL-8 gene expression by IFN-beta represents a hitherto unknown mechanism and target of IFN action.
机译：细胞因子白介素8（IL-8）是嗜中性粒细胞，淋巴细胞和嗜碱细胞趋化性和激活的重要介质。先前我们证明了β干扰素（IFN-β）可以在转录水平上抑制肿瘤坏死因子（TNF）诱导的IL-8基因表达，这显然是通过一种新的机制。为了确定参与这种抑制作用的顺式作用元件和反式作用因子，将包含IL-8基因5'侧翼区部分的DNA构建体与氯霉素乙酰转移酶（CAT）报告基因连接，并转染到人类二倍体中FS-4成纤维细胞。范围从-98到+44的区域足以赋予TNF诱导能力和同时给予IFN-β抑制作用。当仅包含NF-IL-6和NF-κB位点（-94至-70位）的DNA片段被IFN-beta或IFN-alpha抑制时，也观察到TNF-或IL-1诱导的CAT活性的抑制。置于同源或异源最小启动子的上游。 TNF也可以诱导在CAT基因前面包含三份NF-κB元件的构建体，并且该刺激作用也被IFN-β抑制，表明NF-κB元件足以赋予NF-κB抑制作用。干扰素这种抑制作用对IL-8基因的NF-κB位点具有特异性，因为这种抑制作用很少被含有来自HLA-B7基因的NF-κB位点的三个拷贝的构建体所标记。用含有IL-8基因的NF-κB和NF-IL-6结合位点（-101至-63）的探针进行的凝胶位移试验表明，IFN-β处理不会阻断NF-κB的活化蛋白或它们与NF-κB位点结合的能力。但是，在IFN-β存在的情况下，用TNF处理过的细胞的核提取物产生了一条额外的条带，该条带似乎包含NF-κB和NF-IL-6家族的蛋白质成分。 NF-κB位点介导的IFN-β抑制IL-8基因表达代表了迄今为止未知的机制和IFN作用的靶标。

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