Mechanism of minimally modified LDL-mediated induction of serum amyloid A gene in monocyte/macrophage cells.

Mechanism of minimally modified LDL-mediated induction of serum amyloid A gene in monocyte/macrophage cells.
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单核细胞/巨噬细胞中最低限度修饰的 LDL 介导的血清淀粉样蛋白 A 基因诱导机制。

DOI:
10.1089/104454999315637
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发表时间:
1999
影响因子:
3.1
通讯作者:
Ray,A
Ray,A
中科院分区:
生物学4区
文献类型:
--
作者:
Ray,BK;Chatterjee,S;Ray,A

文献摘要

被引文献

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Minimally modified low-density lipoprotein (MM-LDL) is regarded as a major risk factor for the development of atherosclerosis. In this report, we show that this lipoprotein complex can induce expression of an inflammatory protein, serum amyloid A (SAA), in monocyte/macrophage cells, a key cell type implicated in the pathogenesis of atherosclerosis. By promoter function analysis and site-directed mutagenesis, we have located promoter regions responsive to MM-LDL action. Using electrophoretic mobility shift, antibody ablation/supershift, and Western blot assays, we showed that induction of SAA by MM-LDL is mediated via activation of SAS binding factor (SAF) and C/EBP transcription factors. We further show that tamoxifen, a downregulator of CD36, one of the major scavenger receptors which binds MM-LDL, can inhibit MM-LDL-mediated SAA induction in THP-1 cells. This finding suggests that CD36 participates in the manifestation of the inflammatory effects of MM-LDL. Our experiments provide the first evidence for transcription factor activation by MM-LDL.