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

Abstract:

: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.

journal_name

DNA Cell Biol

journal_title

DNA and cell biology

authors

Ray BK,Chatterjee S,Ray A

doi

10.1089/104454999315637

keywords:

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

65-73

issue

1

eissn

1044-5498

issn

1557-7430

journal_volume

18

pub_type

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