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人单核细胞和内皮细胞中组织因子基因表达的调控

Regulation of tissue factor gene expression in human monocytic and endothelial cells.

作者信息

Mackman N

机构信息

Departments of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.

出版信息

Haemostasis. 1996;26 Suppl 1:17-9. doi: 10.1159/000217234.

Abstract

Tissue factor (TF) is inducibly expressed within the vasculature by monocytes and endothelial cells. Transcriptional activation of the TF gene in these two cell types by bacterial lipopolysaccharide (LPS) or cytokines appears to be regulated by a common mechanism. Functional studies identified a 56-bp LPS response element which contains two AP-1 sites and a kappaB site. Assembly of a multiprotein complex composed of Fos-Jun and c-Rel-p65 heterodimers is required to induce TF gene transcription. Inhibiting proteolytic degradation of IkappaBalpha prevents nuclear translocation of c-Rel-p65 heterodimers and blocks inducible TF expression in monocytic and endothelial cells.

摘要

组织因子(TF)由单核细胞和内皮细胞在脉管系统中诱导表达。细菌脂多糖(LPS)或细胞因子对这两种细胞类型中TF基因的转录激活似乎受一种共同机制调控。功能研究鉴定出一个56碱基对的LPS反应元件,其包含两个AP-1位点和一个κB位点。诱导TF基因转录需要由Fos-Jun和c-Rel-p65异二聚体组成的多蛋白复合物的组装。抑制IkappaBalpha的蛋白水解降解可防止c-Rel-p65异二聚体的核转位,并阻断单核细胞和内皮细胞中TF的诱导性表达。

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