Halvorsen Bente, Waehre Torgun, Scholz Hanne, Clausen Ole Petter, von der Thüsen Jan H, Müller Fredrik, Heimli Hilde, Tonstad Serena, Hall Christian, Frøland Stig S, Biessen Erik A, Damås Jan Kristian, Aukrust Pål
Research Institute for Internal Medicine, The National Hospital, Oslo, Norway.
J Lipid Res. 2005 Feb;46(2):211-9. doi: 10.1194/jlr.M400324-JLR200. Epub 2004 Nov 16.
Interleukin (IL)-10 may have a therapeutic potential in atherosclerosis, but its mechanisms of action have not been clarified. Foam cell formation is a key event in atherogenesis, and apoptosis of these lipid-laden cells may promote plaque destabilization. We sought to explore whether IL-10 could have plaque-stabilizing properties in acute coronary syndromes (ACS). We studied the effect of IL-10 on oxidized low density lipoprotein (oxLDL)-stimulated THP-1 cells and monocyte-derived macrophages from ACS patients and healthy controls using different experimental approaches. Our main findings were: i) IL-10 enhances lipid accumulation in oxLDL-stimulated THP-1 macrophages, at least partly by counteracting oxLDL-induced apoptosis; ii) This antiapoptotic effect of IL-10 involves increased expression of the antiapoptotic genes Bfl-1 and Mcl-1, accompanied by protective effects on mitochondria function; iii) By silencing Bfl-1 and Mcl-1 genes using siRNAs, we were able to abolish this IL-10-mediated effect on lipid accumulation; iv) IL-10 also induced lipid accumulation in oxLDL-stimulated macrophages from patients with ACS, but not in macrophages from healthy controls; v) In ACS patients, this enhancing effect of IL-10 on lipid accumulation was accompanied by enhanced Mcl-1 expression. No such antiapoptotic effect was seen in macrophages from healthy controls. These findings suggest a new mechanism for the effect of IL-10 in atherosclerosis, possibly contributing to plaque stabilization.
白细胞介素（IL）-10可能在动脉粥样硬化中具有治疗潜力，但其作用机制尚未阐明。泡沫细胞形成是动脉粥样硬化发生过程中的关键事件，这些脂质负载细胞的凋亡可能促进斑块不稳定。我们试图探究IL-10在急性冠状动脉综合征（ACS）中是否具有斑块稳定特性。我们使用不同的实验方法研究了IL-10对氧化型低密度脂蛋白（oxLDL）刺激的THP-1细胞以及ACS患者和健康对照者单核细胞衍生巨噬细胞的影响。我们的主要发现如下：i）IL-10增强oxLDL刺激的THP-1巨噬细胞中的脂质积累，至少部分是通过抵消oxLDL诱导的细胞凋亡来实现；ii）IL-10的这种抗凋亡作用涉及抗凋亡基因Bfl-1和Mcl-1表达增加，同时对线粒体功能具有保护作用；iii）通过使用小干扰RNA（siRNA）沉默Bfl-1和Mcl-1基因，我们能够消除IL-10介导的对脂质积累的影响；iv）IL-10还诱导ACS患者oxLDL刺激的巨噬细胞中脂质积累，但对健康对照者的巨噬细胞无此作用；v）在ACS患者中，IL-10对脂质积累的这种增强作用伴随着Mcl-1表达增强。在健康对照者的巨噬细胞中未观察到这种抗凋亡作用。这些发现提示了IL-10在动脉粥样硬化中发挥作用的一种新机制，可能有助于斑块稳定。
