Constitutive and interleukin-1 (IL-1)-inducible factors interact with the IL-1-responsive element in the IL-6 gene
Constitutive and interleukin-1 (IL-1)-inducible factors interact with the IL-1-responsive element in the IL-6 gene
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DOI：
10.1128/mcb.10.6.2757-2764.1990
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发表时间：
1990-06
影响因子：
5.3
通讯作者：
H. Isshiki;S. Akira;Osamu Tanabe;Toshihiro Nakajima;T. Shimamoto;T. Hirano;T. Kishimoto
中科院分区：
文献类型：
--
作者：
H. Isshiki;S. Akira;Osamu Tanabe;Toshihiro Nakajima;T. Shimamoto;T. Hirano;T. Kishimoto
白细胞介素-6（IL-6）启动子被其他细胞因子（包括IL-1、肿瘤坏死因子和血小板衍生生长因子）以及佛波醇酯和增加细胞内环AMP的试剂快速和瞬时激活。在这项研究中，我们已经调查了顺式作用的调控元件和反式作用因子负责IL-1诱导IL-6基因的表达。对人IL-6基因5'端缺失突变体的研究表明，IL-1应答元件定位于IL-6启动子区（-180至-123），该启动子区与c-fos血清应答增强子元件同源。凝胶阻滞试验鉴定了两种类型的核因子，一种是组成型的，另一种是诱导型的。这两个因子识别14个碱基对（bp）的回文序列，ACATTGCACAATCT。此外，这个14 bp回文序列的三个拷贝赋予IL-1对无增强子的IL-6启动子的响应性，表明14 bp二联体对称序列是IL-6基因中的IL-1响应元件。
The interleukin-6 (IL-6) promoter is rapidly and transiently activated with other cytokines, including IL-1, tumor necrosis factor, and platelet-derived growth factor, as well as phorbol esters and agents that increase intracellular cyclic AMP. In this study, we have investigated cis-acting regulatory elements and trans-acting factors responsible for IL-1-induced IL-6 gene expression. Studies on the 5' deletion mutants of the human IL-6 gene suggested that the IL-1-responsive element was mapped within the IL-6 promoter region (-180 to -123) which was homologous to the c-fos serum-responsive enhancer element. Gel retardation assay identified two types of nuclear factors that bound to this region, one constitutive and the other inducible. These two factors recognized a 14-base-pair (bp) palindromic sequence, ACATTGCACAATCT. Furthermore, three copies of this 14-bp palindrome conferred IL-1 responsiveness to the basal enhancerless IL-6 promoter, indicating that a 14-bp-dyad symmetry sequence was an IL-1-responsive element in the IL-6 gene.