Effect of IL-10 on LOX-1 expression, signalling and functional activity: An atheroprotective response
Effect of IL-10 on LOX-1 expression, signalling and functional activity: An atheroprotective response
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DOI：
10.1177/1479164113489042
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发表时间：
2013-09-01
影响因子：
2.4
通讯作者：
Chandra, Nimai C.
中科院分区：
文献类型：
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作者：
Arjuman, Albina;Chandra, Nimai C.
凝集素样氧化低密度脂蛋白受体-1（LOX-1）因其在动脉粥样硬化形成中的促炎潜力而受到关注。本研究评估了在存在动脉粥样硬化保护细胞因子白细胞介素-10（IL-10）的情况下LOX-1受体的调节。氧化低密度脂蛋白（oxLDL）和IL-10刺激LOX-1细胞表面表达THP-1巨噬细胞。然而，我们的研究表明oxLDL和IL-10对LOX-1功能的不同作用。oxLDL诱导的LOX-1通过增加细胞内NO（一种促炎过氧亚硝酸盐的底物）促进促炎信号传导。相比之下，IL-10诱导的LOX-1促进细胞外oxLDL的清除，而对促炎信号传导没有任何影响。IL-10的动脉粥样硬化保护作用通过促进细胞oxLDL摄取和LOX-1基因的动脉粥样硬化保护单倍型LOXIN的表达来证明。因此，IL-10的表达增加可能有助于减轻由oxLDL与巨噬细胞上的其同源受体LOX-1相互作用产生的促炎信号发展的动脉粥样硬化的风险。
The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has gained attention for its pro-inflammatory potential in atherogenesis. This study evaluates LOX-1 receptor modulation in the presence of an atheroprotective cytokine, interleukin-10 (IL-10). Both oxidized low-density lipoprotein (oxLDL) and IL-10 stimulated LOX-1 cell surface expression on THP-1 macrophages. However, our study demonstrates differential roles of oxLDL and IL-10 on LOX-1 functionality. Seemingly, oxLDL-induced LOX-1 promoted pro-inflammatory signalling by increasing intracellular NO, a substrate for pro-inflammatory peroxynitrite. In contrast, IL-10-induced LOX-1 facilitated scavenging of extracellular oxLDL without any effect on pro-inflammatory signalling. The atheroprotective effects of IL-10 were demonstrated by both facilitation of cellular oxLDL uptake and expression of LOXIN, an atheroprotective haplotype of the LOX-1 gene. Thus, increased expression of IL-10 may help to attenuate the risk of atherosclerosis developed by pro-inflammatory signal(s) generated through the interaction of oxLDL with its cognate receptor LOX-1 on macrophages.