Intercellular Adhesion Molecule-1 Gene Expression in Human Endothelial Cells
Intercellular Adhesion Molecule-1 Gene Expression in Human Endothelial Cells
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人内皮细胞中细胞间粘附分子 1 基因的表达
DOI：
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
T. Parks
中科院分区：
文献类型：
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作者：
S. Wertheimer;C. L. Myers;R. Wallace;T. Parks
细胞间粘附分子1 （ICAM1）是一种表达于炎症内皮表面的诱导糖蛋白，部分介导粒细胞向感染或损伤部位外渗。在未受刺激的人脐静脉内皮细胞（HUVECs）中未检测到ICAM-1 mRNA，但在肿瘤坏死因子-a （TNF-a）或肉豆蔻酸酯磷酸酯（PMA）处理后，ICAM-1 mRNA会短暂积累，最大稳态水平分别出现在2小时或4小时。PMA预处理HUVECs 72 h可下调蛋白激酶C，抑制PMA随后诱导的ICAM-1 mRNA，但不影响tnf -a诱导的信息积累。核运行试验显示，ICAM-1基因在基础条件下在HUVECs中转录，TNF-a在治疗30分钟内刺激转录活性3至4倍。相比之下，PMA在刺激后4小时内对ICAM-1基因转录几乎没有影响。消息稳定性研究证实，PMA诱导的ICAM-1 mRNA的半衰期比tnf -a诱导的消息更长。这些结果表明，PMA主要通过蛋白激酶C稳定ICAM-1 mRNA，在转录后水平上调ICAM-1的表达，而TNF-a则通过一种未定义的、不依赖于蛋白激酶C的途径转录调节ICAM1基因的表达。
Intercellular adhesion molecule1 (ICAM1) is an inducible glycoprotein expressed on the surface of inflamed endothelium which mediates in part the extravasation of granulocytes into sites of infection or injury. ICAM-1 mRNA is not detected in unstimulated human umbilical vein endothelial cells (HUVECs), but accumulates transiently following tumor necrosis factor-a (TNF-a) or phorbol myristate acetate (PMA) treatment with maximal steady state levels occurring at 2 or 4 h, respectively. Pretreating HUVECs with PMA for 72 h down-regulates protein kinase C and inhibits the subsequent induction of ICAM-1 mRNA by PMA, but does not affect TNF-a-induced message accumulation. Nuclear run-on assays showed that the ICAM-1 gene is transcribed under basal conditions in HUVECs, and that TNF-a stimulates transcriptional activity 3to 4fold within 30 min of treatment. In contrast, PMA has little effect on ICAM-1 gene transcription up to 4 h following stimulation. Message stability studies established that ICAM-1 mRNA induced by PMA has a longer half-life than the TNF-a-induced message. These results suggest that PMA acts through protein kinase C to up-regulate ICAM-1 expression primarily at a post-transcriptional level by stabilizing ICAM-1 mRNA, whereas TNF-a transcriptionally regulates ICAM1 gene expression through an undefined, protein kinase C-independent pathway.