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首页> 外文期刊>Molecular and Cellular Biology >A 58-base-pair region of the human C3 gene confers synergistic inducibility by interleukin-1 and interleukin-6.
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A 58-base-pair region of the human C3 gene confers synergistic inducibility by interleukin-1 and interleukin-6.

机译：人类C3基因的58个碱基对区域通过白介素1和白介素6产生协同诱导作用。

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摘要

We have cloned the promoter for the human third component of complement (C3) gene and have identified sequences involved in its regulation during the acute-phase response. A construct linking 199 bp of the C3 promoter to the firefly luciferase gene was found to be very responsive to interleukin-1 (IL-1) and modestly responsive to interleukin-6 (IL-6) by transfection analysis in the human hepatoma line Hep3B2. Simultaneous treatment with the two cytokines showed a strong synergy between the actions of the two molecules. A 58-bp fragment (-127 to -70 bp) was shown by 5' and 3' deletional mutagenesis to contain cis-acting elements that mediated both the IL-1 response and the IL-1-plus-IL-6 synergistic response of this promoter. When coupled to a heterologous promoter, this fragment enabled the synergistic induction by IL-1 plus IL-6. Sequences homologous to the palindrome ACATTGCACAATCT, which mediates the induction of the IL-6 gene by IL-1 (S. Akira, H. Isshiki, T. Sugita, O. Tanabe, S. Kinoshita, Y. Nishio, T. Nakajima, T. Hirano, and T. Kishimoto, EMBO J. 9:1897-1906, 1990), and the core sequence of the IL-6-responsive element of the rat alpha 2-macroglobulin gene (CTGGGA; M. Hattori, L. J. Abraham, W. Northemann, and G. H. Fey, Proc. Natl. Acad. Sci. USA 87:2364-2368, 1990) are contained within this fragment in immediate juxtaposition and partially overlapping. Site-directed mutagenesis within this homology region drastically reduced the inducibility of the C3 promoter by either cytokine. DNase I footprinting analysis defined a binding site for the transcription factor CCAAT/enhancer-binding protein (C/EBP), which included the IL-1-responsive element-like sequence. No differences were seen between the footprints generated by using extracts from unstimulated and IL-1-stimulated Hep3B2 cells. However, gel retardation analyses revealed two IL-1-specific bands. The data suggest that the induction by IL-1 is mediated by a factor belonging to the family of C/EBP-related proteins.
机译：我们已经克隆了人类补体（C3）基因第三部分的启动子，并确定了在急性期反应中参与其调控的序列。通过在人类肝癌细胞系Hep3B2中进行转染分析，发现将199 bp的C3启动子连接至萤火虫荧光素酶基因的构建体对白介素1（IL-1）非常敏感，对白介素6（IL-6）具有中等响应。 。用两种细胞因子同时处理显示两种分子的作用之间有很强的协同作用。通过5'和3'缺失诱变显示58 bp的片段（-127至-70 bp）包含顺式作用元件，该元件介导IL-1应答和IL-1-plus-IL-6协同应答。该启动子。当与异源启动子偶联时，该片段使得能够由IL-1和IL-6协同诱导。与回文ACATTGCACAATCT同源的序列，介导IL-1对IL-6基因的诱导（S. Akira，H.Ishiki，T。Sugita，O。Tanabe，S。Kinoshita，Y。Nishio，T。Nakajima， T. Hirano和T. Kishimoto，EMBO J. 9：1897-1906，1990），以及大鼠α2-巨球蛋白基因的IL-6响应元件的核心序列（CTGGGA; M。Hattori，LJ亚伯拉罕） ，W.Northemann，和GHFey，Proc.Natl.Acad.Sci.USA 87：2364-2368，1990）以立即并置和部分重叠的方式包含在该片段内。在该同源区域内的定点诱变极大地降低了任一细胞因子对C3启动子的诱导性。 DNase I足迹分析定义了转录因子CCAAT /增强子结合蛋白（C / EBP）的结合位点，其中包括IL-1反应元件样序列。使用未刺激和IL-1刺激的Hep3B2细胞提取物产生的足迹之间没有差异。然而，凝胶阻滞分析揭示了两个IL-1特异性条带。数据表明，IL-1的诱导是由属于C / EBP相关蛋白家族的因子介导的。

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