ACTIVATION OF THE HUMAN BETA-2-INTERFERON HEPATOCYTE-STIMULATING FACTOR INTERLEUKIN-6 PROMOTER BY CYTOKINES, VIRUSES, AND 2ND MESSENGER AGONISTS
ACTIVATION OF THE HUMAN BETA-2-INTERFERON HEPATOCYTE-STIMULATING FACTOR INTERLEUKIN-6 PROMOTER BY CYTOKINES, VIRUSES, AND 2ND MESSENGER AGONISTS
复制标题
DOI：
10.1073/pnas.85.18.6701
复制
发表时间：
1988-09-01
影响因子：
11.1
通讯作者：
SEHGAL, PB
中科院分区：
文献类型：
--
作者：
RAY, A;TATTER, SB;SEHGAL, PB
“β 2-干扰素（IFN-β 2）/肝细胞刺激因子/白细胞介素6”基因表达的标志是其在不同类型的人细胞（成纤维细胞、单核细胞、上皮细胞和内皮细胞）中被不同刺激物诱导，所述刺激物包括细胞因子如肿瘤坏死因子、白细胞介素1（IL-1）和血小板衍生生长因子、不同病毒和细菌产物如内毒素。在转染到HeLa细胞中后，研究了细胞因子、病毒和第二信使激动剂对与细菌氯霉素乙酰转移酶（CAT）基因连接的β-FN-β 2启动子的激活。含有从-1180到+13的IFN-β 2 DNA的嵌合基因与CAT基因相连，是可诱导的。10-佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）的作用增加一倍，其次是伪狂犬病病毒和仙台病毒，（各7- 11倍）;血清（6- 9倍）;细胞因子肿瘤坏死因子、IL-1和表皮生长因子（各3至5倍）; cAMP激动剂BrcAMP和毛喉素和磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤（各2至6倍）;聚（I）.聚（C）（2- 4倍）; 1，2-二酰基甘油和钙离子载体A23187（各1.5- 2倍）。在HeLa细胞中，细菌内毒素不激活该IFN-β 2/CAT融合基因。在融合基因中IFN-β 2 DNA的5“边界从-1180到-596的缺失保留了其被IL-1、肿瘤坏死因子、表皮生长因子、血清、伪狂犬病和仙台病毒以及PMA、Br-cAMP和毛喉素的激活;缺失到-225导致对血清、PMA和仙台病毒的反应性的小幅度降低（因子1.5-2），但对其它诱导剂的反应性不降低;进一步缺失到-112大大降低了所有的反应性。因此，IFN-β 2中-225和-113之间的区域，其含有与人c-fos基因中的调节元件相似的DNA基序，似乎含有负责通过几种不同的细胞因子、病毒和第二信使激动剂激活IFN-β 2启动子的主要顺式作用调节元件。
The hallmark of ".beta.2-interferon (IFN-.beta.2)/hepatocyte-stimulating factor/interleukin 6" gene expression is its inducibility in different types of human cells (fibroblasts, monocytes, epithelial cells, and endothelial cells) by different stimuli, which include cytokines such as tumor necrosis factor, interleukin 1 (IL-1) and platelet-derived growth factor, different viruses, and bacterial products such as endotoxin. The activation by cytokines, viruses, and second messenger agonists of the (FN-.beta.2 promoter linked to the bacterial chloramphenicol acetyltransferase (CAT) gene was studied after transfection into HeLa cells. A chimeric gene containing IFN-.beta.2 DNA from -1180 to +13 linked to the CAT gene was inducible .apprxeq. 10-fold by phorbol 12-myristate 13-acetate (PMA), followed, in decreasing order, by pseudorabies and Sendai viruses (7- to 11-fold each); serum (6- to 9-fold); the cytokines tumor necrosis factor, IL-1, and epidermal growth factor (3- to 5-fold each); the cAMP agonists BrcAMP and forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (2- to 6-fold each); poly(I) .cntdot. poly(C) (2- to 4-fold); 1,2-diacylglycerol and the calcium ionophore A23187 (1.5- to 2-fold each). Bacterial endotoxin did not activate this IFN-.beta.2/CAT fusion gene in HeLa cells. Deletion of the 5'' boundary of the IFN-.beta.2 DNA from -1180 to -596 in the fusion gene preserved its activation by IL-1, tumor necrosis factor, epidermal growth factor, serum, pseudorabies, and Sendai viruses and by PMA, Br-cAMP, and forskolin; deletion to -225 led to a small reduction (by a factor of 1.5-2) in the responsiveness to serum, PMA, and Sendai virus but not to the other inducers; a further deletion to -112 greatly reduced all responsiveness. Thus, the region between -225 and -113 in IFN-.beta.2, which contains DNA motifs similar to the regulatory elements in the human c-fos gene, appears to contain the major cis-acting regulatory elements responsible for the activation of the IFN-.beta.2 promoter by several different cytokines, viruses, and second messenger agonists.