Transforming growth factor-beta 1 inhibits scavenger receptor activity in THP-1 human macrophages.
Transforming growth factor-beta 1 inhibits scavenger receptor activity in THP-1 human macrophages.
复制标题
DOI：
10.1016/s0021-9258(18)54434-3
复制
发表时间：
1991-12
期刊：
影响因子：
--
通讯作者：
L. Bottalico;R. E. Wager;L. Agellon;R. Assoian;Ira Tabas
中科院分区：
文献类型：
--
作者：
L. Bottalico;R. E. Wager;L. Agellon;R. Assoian;Ira Tabas
巨噬细胞清道夫受体是一种220 kDa的三聚体膜糖蛋白，介导修饰形式的低密度脂蛋白（LDL）如乙酰-LDL和氧化-LDL的内化，因此可能在动脉粥样硬化巨噬细胞泡沫细胞形成中发挥关键作用。此外，最近的证据表明，清道夫受体可能是一个重要的巨噬细胞结合位点的脂多糖参与巨噬细胞清除脂多糖。然而，对这一重要受体的调控知之甚少。我们现在报告，诱导清道夫受体活性（通过乙酰-LDL刺激细胞内胆固醇酯化）在佛波酯分化的THP-1人巨噬细胞中观察到的被完全抑制的水平，在未分化的THP-1单核细胞中看到的皮摩尔浓度的转化生长因子-β 1（TGF-β 1）。TGF-β 1以剂量依赖性方式抑制125 I-乙酰基-LDL降解，最大抑制（约70%）发生在24 pM TGF-β 1。Scatchard分析显示，TGF-β 1处理导致受体数量减少约2倍，从分化的THP-1巨噬细胞分离的RNA的北方印迹分析表明，与未用TGF-β 1处理的巨噬细胞相比，TGF-β 1处理的细胞中清道夫受体mRNA减少约2倍。由于TGF-β 1被认为存在于动脉粥样硬化和炎性病变中，上述发现可能与调节粥样硬化泡沫细胞形成和/或调节巨噬细胞清除脂多糖有关。
The macrophage scavenger receptor, a 220-kDa trimeric membrane glycoprotein, mediates the internalization of modified forms of low density lipoprotein (LDL) such as acetyl-LDL and oxidized-LDL and thus is likely to play a key role in atheroma macrophage foam cell formation. In addition, recent evidence suggests that the scavenger receptor may be an important macrophage binding site for lipopolysaccharide involved in lipopolysaccharide scavenging by macrophages. However, little is known about the regulation of this important receptor. We now report that the induction of scavenger receptor activity (as measured by acetyl-LDL stimulation of intracellular cholesterol esterification) seen in phorbol ester-differentiated THP-1 human macrophages was completely suppressed to the level seen in undifferentiated THP-1 monocytes by picomolar concentrations of transforming growth factor-beta 1 (TGF-beta 1). 125I-Acetyl-LDL degradation was inhibited in a dose-dependent manner by TGF-beta 1, with maximal inhibition (approximately 70%) occurring at 24 pM TGF-beta 1. Scatchard analysis revealed that TGF-beta 1 treatment resulted in a approximately 2-fold decrease in receptor number, and Northern blot analysis of RNA isolated from differentiated THP-1 macrophages demonstrated approximately 2-fold less scavenger receptor mRNA in TGF-beta 1-treated cells compared with that in macrophages not treated with TGF-beta 1. Since TGF-beta 1 is thought to be present in both atherosclerotic and inflammatory lesions, the above findings may have physiological relevance regarding the regulation of atheroma foam cell formation and/or the regulation of lipopolysaccharide clearance by macrophages.