INVOLVEMENT OF A NF-KAPPA-B-LIKE TRANSCRIPTION FACTOR IN THE ACTIVATION OF THE INTERLEUKIN-6 GENE BY INFLAMMATORY LYMPHOKINES
INVOLVEMENT OF A NF-KAPPA-B-LIKE TRANSCRIPTION FACTOR IN THE ACTIVATION OF THE INTERLEUKIN-6 GENE BY INFLAMMATORY LYMPHOKINES
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DOI：
10.1128/mcb.10.2.561
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发表时间：
1990-02-01
影响因子：
5.3
通讯作者：
YAMAMOTO, K
中科院分区：
文献类型：
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作者：
SHIMIZU, H;MITOMO, K;YAMAMOTO, K
白细胞介素-6（IL-6）是炎症的主要介质之一，其表达可由其它炎性淋巴因子白细胞介素-1（IL-1）和肿瘤坏死因子α诱导。（TNF-α）。我们证明了一个共同的IL-6启动子元件，称为炎性淋巴因子应答元件（ILRE），对于IL-1和TNF-α诱导IL-6基因表达是重要的。尽管这些淋巴因子的作用机制可能存在差异。值得注意的是，位于相对于mRNA帽位点的-73至-63之间的ILRE序列与NF-κ B转录因子结合基序高度同源，并结合IL-1-TNF-α-B。诱导核因子;该因子的序列特异性、结合特征和亚细胞定位与NF-κ B的序列特异性、结合特征和亚细胞定位不可区分。此外，ILRE序列的突变损害了该核因子的结合，从而消除了IL-1和TNF-α对IL-6基因表达的诱导。in vivo.这些结果表明，与NK-κ B不可区分的核因子参与IL-1和TNF-α对IL-6基因的转录激活。
Interleukin-6 (IL-6) is one of the major mediators of inflammation, and its expression is inducible by the other inflammatory lymphokines, interleukin-1 (IL-1) and tumor necrosis factor .alpha. (TNF-.alpha.). We demonstrate that a common IL-6 promoter element, termed inflammatory lymphokine-responsive element (ILRE), is important for induction of IL-6 gene expression by IL-1 and TNF-.alpha. despite possible differences in the mechanisms of action of these lymphokines. Remarkably, the ILRE sequence, located between -73 to -63 relative to the mRNA cap site, is highly homologous to NF-.kappa.B transcription factor-binding motifs and binds an IL-1-TNF-.alpha.-inducible nuclear factor; the sequence specificities, binding characteristics, and subcellular localizations of this factor are indistinguishable from those of NF-.kappa.B. In addition, mutations of the ILRE sequence which impair the binding of this nuclear factor abolished the induction of IL-6 gene expression by IL-1 and TNF-.alpha. in vivo. These results indicate that a nuclear factor indistinguishable from NK-.kappa.B is involved in the transcriptional activation of the IL-6 gene by IL-1 and TNF-.alpha.