Silencing Triggering Receptors Expressed on Myeloid Cells-1 Impaired the Inflammatory Response to Oxidized Low-Density Lipoprotein in Macrophages
Silencing Triggering Receptors Expressed on Myeloid Cells-1 Impaired the Inflammatory Response to Oxidized Low-Density Lipoprotein in Macrophages
复制标题
沉默髓样细胞-1 上表达的触发受体会损害巨噬细胞中氧化低密度脂蛋白的炎症反应。
DOI：
10.1007/s10753-015-0239-5
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发表时间：
2016-02-01
期刊：
影响因子：
5.1
通讯作者：
Yan, Fuhua
中科院分区：
文献类型：
--
作者：
Li, Houxuan;Hong, Feifei;Yan, Fuhua
动脉粥样硬化是一种慢性进行性炎症性疾病，其特征在于动脉壁中脂质含量的积聚。以往的研究表明，Toll样受体（TLR）参与了血管壁脂质沉积和炎症反应。髓样细胞上表达的触发受体1（TREM-1）是免疫球蛋白超家族的细胞表面受体，其放大TLR途径的信号转导并增强对微生物感染的免疫应答。本研究的目的是研究氧化低密度脂蛋白（oxLDL）对TREM-1表达的影响，以及其参与RAW264.7小鼠巨噬细胞中促炎细胞因子的产生和泡沫细胞的形成。oxLDL增强巨噬细胞中TREM-1和TLR-4的基因表达，但不增强TLR-2的基因表达;此外，通过短发夹干扰RNA沉默TREM-1的表达可抑制脂质吞噬和促炎性肿瘤坏死因子-α（TNF-α）以及白细胞介素-6（IL-6）的产生;此外，应用合成拮抗剂LP-17多肽在体外和体内减少oxLDL刺激时IL-6的产生。总之，在巨噬细胞中，oxLDL增强了TREM-1的表达，从而放大了TLR途径的先天免疫应答; TREM-1的激活通过增强促炎细胞因子的产生和泡沫细胞的形成而有助于动脉粥样硬化形成过程。
Atherosclerosis is a chronic progressive inflammatory disease characterized by the accumulation of lipid contents in arterial walls. Previous studies suggest participation of Toll-like receptors (TLRs) in lipid deposition and inflammatory response in vascular wall. The triggering receptor expressed on myeloid cells 1 (TREM-1) is a cell surface receptor of the immunoglobulin superfamily, which amplifies signal transduction of TLR pathway and enhances immune response to microbial infections. The aim of the present study was to investigate the effect of the oxidized low-density lipoprotein (oxLDL) on the expression of the TREM-1, as well as its engagement in proinflammatory cytokine production and foam cell formation in RAW264.7 mice macrophages. oxLDL enhanced TREM-1 and TLR-4, but not TLR-2 gene expression in macrophages; furthermore, silencing TREM-1 expression by short hairpin interfering RNA inhibited lipid phagocytosis and proinflammatory tumor necrosis factor-alpha (TNF-alpha) as well as interleukin-6 (IL-6) production in macrophages; moreover, application of synthetic antagonist, LP-17 polypeptide, reduced IL-6 production upon oxLDL stimulation in vitro and in vivo. In conclusion, in macrophages, oxLDL enhanced expression of TREM-1, which amplifies the innate immune response of TLR pathway; activation of TREM-1 contributes to atherogenesis process by enhancing proinflammatory cytokine production and foam cell formation.