Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8.
Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8.
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DOI：
10.4049/jimmunol.143.4.1366
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发表时间：
1989-08
影响因子：
4.4
通讯作者：
N. Mukaida;M. Shiroo;K. Matsushima
中科院分区：
文献类型：
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作者：
N. Mukaida;M. Shiroo;K. Matsushima
为了确定基因表达的可能调控位点，我们克隆了人单核细胞源性中性粒细胞趋化因子（MDNCF/IL-8）的基因组DNA，其mRNA可由IL-1或TNF诱导，并确定了其全核苷酸序列。结果表明，MDNCF/IL-8基因由4个外显子和3个内含子组成，具有单一的“CAT”和“TATA”样结构。MDNCF/IL-8基因的5'-侧翼区域与其他细胞因子和急性期反应物基因的整体序列没有相似性，这些基因的产生也受IL-1和TNF的影响。然而，5'侧区含有几种核因子的潜在结合位点，包括活化因子-1、活化因子-2、IFN调节因子-1和肝细胞核因子-1。此外，糖皮质激素响应元件和热休克元件位于5′侧区。由于PMA诱导MDNCF/IL-8 mRNA在人PBMC中积累，而糖皮质激素抑制LPS诱导MDNCF/IL-8 mRNA的表达，该基因的表达可能是通过这些核因子与5'侧DNA的相互作用来调节的。
To identify possible regulatory sites of the gene expression, we cloned the genomic DNA of human monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8), whose mRNA is induced by IL-1 or TNF and determined its entire nucleotide sequence. The results show that the MDNCF/IL-8 gene consists of 4 exons and 3 introns with a single "CAT"- and "TATA"-like structure. The 5'-flanking region of MDNCF/IL-8 gene shows no overall sequence similarity with that of other cytokine and acute phase reactant genes whose production is also affected by IL-1 and TNF. The 5' flanking region, however, contains potential binding sites for several nuclear factors including activation factor-1, activation factor-2, IFN regulatory factor-1, and hepatocyte nuclear factor-1. In addition, the glucocorticoid responsive element and heat shock element were located in the 5'-flanking region. Inasmuch as PMA induces MDNCF/IL-8 mRNA accumulation in human PBMC and a glucocorticoid inhibits the induction of MDNCF/IL-8 mRNA by LPS, the expression of this gene is probably regulated by interaction of these nuclear factors with the 5'-flanking DNA.