Identification of a γ-interferon-responsive element in the promoter of the human macrophage scavenger receptor A gene

被引:34
作者
Grewal, T [1 ]
Priceputu, E [1 ]
Davignon, J [1 ]
Bernier, L [1 ]
机构
[1] Clin Res Inst Montreal, Hyperlipidemia & Atherosclerosis Res Grp, Montreal, PQ H2W 1R7, Canada
关键词
scavenger receptor type A; gamma-interferon; STAT1; alpha; GAS element; macrophage activation;
D O I
10.1161/01.ATV.21.5.825
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In the present study, we demonstrate gamma -interferon (gamma -IFN)-inducible scavenger receptor A (SR-A) mRNA expression during the early stages of THP-1 and blood monocyte differentiation. Predominant induction of SR-A type II mRNA parallels the increased accumulation of cholesteryl esters under these conditions. A potential signal transducer and activator of transcription (STAT1) binding site (gamma -interferon activation site) in the SR-A promoter demonstrates gamma -IFN-inducible DNA binding activity and is most likely responsible for the gamma -IFN-dependent expression of an SR-A promoter-luciferase fusion construct. In contrast, gamma -IFN inhibits SR-A expression in mature macrophages as well as after prolonged gamma -IFN incubation of THP-1 monocytes. Taken together, these results demonstrate opposite effects of gamma -IFN on SR-A expression and activity during the early versus late stages of monocyte maturation. gamma -IFN-induced STAT1 activation, leading to increased SR-A expression, could therefore play an important role in the initial steps of foam cell formation and xanthomatosis.
引用
收藏
页码:825 / 831
页数:7
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