Viperin Deficiency Promotes Polarization of Macrophages and Secretion of M1 and M2 Cytokines.

Viperin Deficiency Promotes Polarization of Macrophages and Secretion of M1 and M2 Cytokines.
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DOI:
10.4110/in.2018.18.e32
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发表时间:
2018-08
期刊:
影响因子:
6
通讯作者:
Seo JY
Seo JY
中科院分区:
医学3区
文献类型:
--
作者:
Eom J;Yoo J;Kim JJ;Lee JB;Choi W;Park CG;Seo JY

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蝰蛇蛋白是一种多功能蛋白质,首先在用干扰素-γ处理的人原代巨噬细胞和感染人巨细胞病毒的人成纤维细胞中鉴定。当在多种细胞如成纤维细胞、肝细胞和免疫细胞(包括T细胞和树突细胞)中诱导时,该蛋白质起到抗病毒蛋白和细胞信号传导途径或细胞代谢的调节剂的作用。然而,蝰蛇蛋白在巨噬细胞中的作用尚不清楚。在这里,我们表明,蝰蛇蛋白是基础上表达的小鼠骨髓细胞,包括单核细胞。其表达在骨髓单核细胞衍生的巨噬细胞(BMDM)中维持,这取决于巨噬细胞集落刺激因子(M-CSF)处理,但不取决于粒细胞-巨噬细胞集落刺激因子(GM-CSF)处理。在用M-CSF或G-MCSF分化的野生型(WT)和蝰蛇蛋白敲除(KO)BMDM中,在M1和M2巨噬细胞标志物(如诱导型一氧化氮合酶(iNOS)和谷胱甘肽转移酶-1)以及细胞因子(如IL-6和IL-10)的基因表达水平上几乎没有差异,表明BMDM中蝰蛇蛋白表达不影响巨噬细胞标志物和细胞因子的基础基因表达。然而,当BMDM完全极化时,蝰蛇蛋白KO M1和M2巨噬细胞中巨噬细胞标志物的表达和细胞因子的分泌水平显著高于WT M1和M2巨噬细胞中的水平。这些数据表明,蝰蛇蛋白在巨噬细胞的极化和M1和M2细胞因子的分泌中起着调节剂的作用。
Viperin is a multifunctional protein that was first identified in human primary macrophages treated with interferon-γ and in human fibroblasts infected with human cytomegalovirus. This protein plays a role as an anti-viral protein and a regulator of cell signaling pathways or cellular metabolism when induced in a variety of cells such as fibroblasts, hepatocytes and immune cells including T cells and dendritic cells. However, the role of viperin in macrophages is unknown. Here, we show that viperin is basally expressed in murine bone marrow cells including monocytes. Its expression is maintained in bone marrow monocyte-derived macrophages (BMDMs) depending on macrophage colony-stimulating factor (M-CSF) treatment but not on granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment. In wild type (WT) and viperin knockout (KO) BMDMs differentiated with M-CSF or G-MCSF, there are little differences at the gene expression levels of M1 and M2 macrophage markers such as inducible nitric oxide synthase (iNOS) and arginase-1, and cytokines such as IL-6 and IL-10, indicating that viperin expression in BMDMs does not affect the basal gene expression of macrophage markers and cytokines. However, when BMDMs are completely polarized, the levels of expression of macrophage markers and secretion of cytokines in viperin KO M1 and M2 macrophages are significantly higher than those in WT M1 and M2 macrophages. The data suggest that viperin plays a role as a regulator in polarization of macrophages and secretion of M1 and M2 cytokines.
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