INTERLEUKIN-1 REGULATES SYNTHESIS OF AMYLOID BETA-PROTEIN PRECURSOR MESSENGER-RNA IN HUMAN-ENDOTHELIAL CELLS
INTERLEUKIN-1 REGULATES SYNTHESIS OF AMYLOID BETA-PROTEIN PRECURSOR MESSENGER-RNA IN HUMAN-ENDOTHELIAL CELLS
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DOI：
10.1073/pnas.86.19.7606
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发表时间：
1989-10-01
影响因子：
11.1
通讯作者：
GAJDUSEK, DC
中科院分区：
文献类型：
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作者：
GOLDGABER, D;HARRIS, HW;GAJDUSEK, DC
我们分析了人脐静脉内皮细胞(HUVEC)中淀粉样β蛋白前体(APP)基因表达的调控。随着人脐静脉内皮细胞融合，APP基因转录水平逐渐升高。在融合培养中，APP基因的半衰期为4小时。人重组白介素1(IL-1)、佛波酯13-乙酸酯或肝素结合生长因子1可促进APP基因的表达，而钙离子载体A23187和地塞米松对此无影响。蛋白激酶C抑制剂1-异喹诺磺酰基-2-甲基哌嗪(H7)可抑制IL-1诱导的APP转录水平的升高。为了定位APP启动子的IL-1反应元件，将APP启动子的截短部分与人类生长激素报告基因融合。将重组质粒导入小鼠神经母细胞瘤细胞，检测细胞培养上清液中人生长激素的含量。位于转录起始点上游-485和-305之间的APP启动子的一个180bp的区域对于IL-1介导的报告基因的诱导是必需的。该区域包含上游转录因子AP-1结合位点。这些结果表明，IL-1通过利用APP启动子的上游AP-1结合位点，通过蛋白激酶C介导的途径上调HUVEC中APP基因的表达。
We have analyzed the modulation of amyloid .beta.-protein precursor (APP) gene expression in human umbilical vein endothelial cells (HUVEC). The level of the APP mRNA transcripts increased as HUVEC reached confluency. In confluent culture the half-life of the APP mRNA was 4 hr. Treatment of the cells with human recombinant interleukin 1 (IL-1), phorbol 12-myristate 13-acetate, or heparin-binding growth factor 1 enhanced the expression of APP gene in these cells, but calcium ionophore A23187 and dexamethasone did not. The protein kinase C inhibitor 1-(isoquinolinsulfonyl)-2-methylpiperazine (H7) inhibited IL-1-mediated increase of the level of APP transcripts. To map IL-1-responsive elements of the APP promoter, truncated portions of the APP promoter were fused to the human growth hormone reporter gene. The recombinant plasmids were transfected into mouse neuroblastoma cells, and the cell medium was assayed for the human growth hormone. A 180-base-pair region of the APP promoter located between position -485 and -305 upstream from the transcription start site was necessary for IL-1-mediated induction of the reportor gene. This region contains the upstream transcription factor AP-1 binding site. These results suggest that IL-1 upregulates APP gene expression in HUVEC through a pathway mediated by protein kinase C, utilizing the upstream AP-1 binding site of the APP promoter.