Viral activation of interleukin-15 (IL-15): Characterization of a virus-inducible element in the IL-15 promoter region

Viral activation of interleukin-15 (IL-15): Characterization of a virus-inducible element in the IL-15 promoter region
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DOI:
10.1128/jvi.74.16.7338-7348.2000
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发表时间:
2000-08-01
影响因子:
5.4
通讯作者:
Waldmann, TA
Waldmann, TA
中科院分区:
医学2区
文献类型:
--
作者:
Azimi, N;Tagaya, Y;Waldmann, TA

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我们在白介素15(IL-15)启动子中的一个核因子-kappa B结合部位上游发现了一个干扰素调节因子基序(IRF-E)。由于这两个基序是β干扰素启动子的病毒诱导增强子区域的一部分,我们推测这两个基因可能对病毒等刺激有类似的反应。为了验证这一假设,用新城疫病毒(NDV)感染L929细胞,诱导IL-15mRNA和蛋白的表达。使用IL-15启动子-报告缺失构建体,病毒诱导区被定位到相对于转录起始点的-295到-233位置,该区域包括IRF-E、NF-kappa B和这两个基序两侧的13个核苷酸序列。通过共转染研究表明,这三个基序都是获得IRF-1和NF-kappa B表达载体诱导的最大启动子活性所必需的。IL-15启动子中病毒可诱导区的存在提示了IL-15作为宿主抗病毒防御机制的一个组成部分的作用。
We identified an interferon regulatory factor motif (IRF-E) upstream of an NF-kappa B binding site in the interleukin-15 (IL-15) promoter. Since these two motifs are part of the virus-inducible enhancer region of the beta interferon promoter, we speculated that there might be similar responses of these two genes to stimuli such as viruses. To test this hypothesis, L929 cells were infected with Newcastle disease virus (NDV), which led to the induction of IL-15 mRNA and protein expression. Using IL-15 promoter-reporter deletion constructs, a virus-inducible region, encompassing IRF-E, NF-kappa B, and a 13-nucleotide sequence flanked by these two motifs, was mapped to the -295-to--233 position relative to the transcription initiation site. Using cotransfection studies, it was demonstrated that all three motifs were essential to achieve the maximum promoter activity induced by IRF-1 and NF-kappa B expression plasmids. The presence of a virus-inducible region in the IL-15 promoter suggests a role for IL-15 as a component of host antiviral defense mechanisms.