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PKCδ对于人源和鼠源巨噬细胞摄取 oxLDL 和泡沫细胞的形成并非必需。

PKCδ is dispensible for oxLDL uptake and foam cell formation by human and murine macrophages.

机构信息

Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, Amsterdam 1066CX, The Netherlands

Department of Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

Cardiovasc Res. 2014 Dec 1;104(3):467-76. doi: 10.1093/cvr/cvu213. Epub 2014 Sep 24.

Abstract

AIMS

Uptake of oxidized lipoprotein particles (oxLDL) and foam cell formation by macrophages is one of the first steps in the development of atherosclerosis. Recently, protein kinase C δ (PKCδ) has been implicated as a regulator of oxLDL uptake and foam cell formation via down-regulation of PKCβ and scavenger receptors CD36 and SR-A expression. Here, we describe studies in which we have re-evaluated the role of PKCδ in oxLDL uptake and foam cell formation.

METHODS AND RESULTS

PKCδ expression was silenced in the human monocytic cell lines and also in primary human monocytes to analyse oxLDL uptake and CD36 expression. Additionally, bone marrow-derived macrophages of PKCδ knockout mice and macrophages cultured from patients with rare null mutations in the PRKCD gene were tested for uptake of oxLDL and foam cell formation. Expression of scavenger receptor CD36 was determined and levels of PKCβ isoforms were quantified. Neither a reduction in PKCδ levels nor its complete absence resulted in a detectable effect on the uptake of oxLDL and the formation of foam cells.

CONCLUSION

PKCδ is dispensible for oxLDL uptake and foam cell formation by monocytes and macrophages.

摘要

目的

氧化型脂蛋白颗粒(oxLDL)被巨噬细胞摄取并形成泡沫细胞是动脉粥样硬化发生的早期步骤之一。最近的研究表明蛋白激酶 C δ(PKCδ)通过下调蛋白激酶 Cβ(PKCβ)和清道夫受体 CD36 和清道夫受体 A(SR-A)的表达,调节 oxLDL 的摄取和泡沫细胞的形成。在此,我们重新评估了 PKCδ 在 oxLDL 摄取和泡沫细胞形成中的作用。

方法和结果

沉默人单核细胞系和原代人单核细胞中的 PKCδ 表达,分析 oxLDL 的摄取和 CD36 的表达。此外,还检测了 PKCδ 基因敲除小鼠的骨髓来源的巨噬细胞和 PRKCD 基因突变患者的巨噬细胞培养物对 oxLDL 的摄取和泡沫细胞的形成。测定了清道夫受体 CD36 的表达水平,并对 PKCβ 同工型的水平进行了定量。PKCδ 水平的降低或完全缺失均未对 oxLDL 的摄取和泡沫细胞的形成产生明显影响。

结论

PKCδ 对于单核细胞和巨噬细胞摄取 oxLDL 和形成泡沫细胞是可有可无的。

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