Identification of a γ-interferon-responsive element in the promoter of the human macrophage scavenger receptor A gene
Identification of a γ-interferon-responsive element in the promoter of the human macrophage scavenger receptor A gene
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DOI：
10.1161/01.atv.21.5.825
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发表时间：
2001-05-01
影响因子：
8.7
通讯作者：
Bernier, L
中科院分区：
文献类型：
--
作者：
Grewal, T;Priceputu, E;Bernier, L
在本研究中，我们证明γ-干扰素（γ-IFN）诱导的清道夫受体A（SR-A）mRNA的表达在THP-1和血液单核细胞分化的早期阶段。在这些条件下，SR-A II型mRNA的主导诱导与胆固醇酯积累增加平行。SR-A启动子中潜在的信号转导子和转录激活子（STAT 1）结合位点（γ-干扰素激活位点）显示γ-IFN诱导型DNA结合活性，并且最可能负责SR-A启动子-荧光素酶融合构建体的γ-IFN依赖性表达。相比之下，γ-IFN抑制成熟巨噬细胞中以及THP-1单核细胞长时间γ-IFN孵育后的SR-A表达。总之，这些结果表明γ-IFN在单核细胞成熟的早期与晚期对SR-A表达和活性的相反作用。γ-IFN-诱导的STAT 1活化导致SR-A表达增加，因此在泡沫细胞形成和黄瘤病的初始步骤中起重要作用。
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.