Different responses to oxidized low-density lipoproteins in human polarized macrophages.
Different responses to oxidized low-density lipoproteins in human polarized macrophages.
复制标题
对人两极化巨噬细胞中氧化的低密度脂蛋白的反应不同。
DOI：
10.1186/1476-511x-10-1
复制
发表时间：
2011-01-04
影响因子：
4.5
通讯作者：
Daida H
中科院分区：
文献类型：
--
作者：
Hirose K;Iwabuchi K;Shimada K;Kiyanagi T;Iwahara C;Nakayama H;Daida H
氧化低密度脂蛋白（oxLDL）被巨噬细胞摄取在泡沫细胞形成中起重要作用。已经表明在人类动脉粥样硬化病变中存在异质性巨噬细胞亚群，如M1和M2。为了评估哪些类型的巨噬细胞有助于动脉粥样硬化形成，我们进行了cDNA微阵列分析，以确定oxLDL诱导的转录改变的每个子集的巨噬细胞。人单核细胞衍生的巨噬细胞向M1或M2亚群极化，然后用oxLDL处理。然后通过cDNA微阵列分析和定量实时RT-PCR评估oxLDL处理期间每个巨噬细胞亚群中的基因表达水平。在高级上调基因和功能本体方面，在M2巨噬细胞中oxLDL处理期间的改变与非极化巨噬细胞（M0）中的改变相似。分子网络分析显示，oxLDL诱导的M1巨噬细胞最高评分分子网络中的大部分分子与转化生长因子（TGF）-β1直接或间接相关。层次聚类分析显示，在所有的巨噬细胞亚群，其中一些含有抗氧化反应元件（ARE）在其启动子区的基因普遍上调。在M1巨噬细胞中特异性上调的一组基因包括与B细胞中κ轻链多肽基因增强子（NF-κB）信号通路的核因子相关的编码分子。实时荧光定量RT-PCR结果显示，oxLDL处理后M2巨噬细胞IL-8基因表达明显低于M0和M1细胞。即使在oxLDL处理后，HMOX 1基因表达水平在所有3个巨噬细胞亚群中几乎相同。本研究表明，在氧化低密度脂蛋白治疗极化巨噬细胞的转录改变。这些数据表明，oxLDL摄取可能影响M1巨噬细胞TGF-β1和NF-κ B介导的功能，但不影响M0或M2巨噬细胞的功能。M1巨噬细胞可能对oxLDL有特征性反应。
Oxidized low-density lipoprotein (oxLDL) uptake by macrophages plays an important role in foam cell formation. It has been suggested the presence of heterogeneous subsets of macrophage, such as M1 and M2, in human atherosclerotic lesions. To evaluate which types of macrophages contribute to atherogenesis, we performed cDNA microarray analysis to determine oxLDL-induced transcriptional alterations of each subset of macrophages. Human monocyte-derived macrophages were polarized toward the M1 or M2 subset, followed by treatment with oxLDL. Then gene expression levels during oxLDL treatment in each subset of macrophages were evaluated by cDNA microarray analysis and quantitative real-time RT-PCR. In terms of high-ranking upregulated genes and functional ontologies, the alterations during oxLDL treatment in M2 macrophages were similar to those in nonpolarized macrophages (M0). Molecular network analysis showed that most of the molecules in the oxLDL-induced highest scoring molecular network of M1 macrophages were directly or indirectly related to transforming growth factor (TGF)-β1. Hierarchical cluster analysis revealed commonly upregulated genes in all subset of macrophages, some of which contained antioxidant response elements (ARE) in their promoter regions. A cluster of genes that were specifically upregulated in M1 macrophages included those encoding molecules related to nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) signaling pathway. Quantitative real-time RT-PCR showed that the gene expression of interleukin (IL)-8 after oxLDL treatment in M2 macrophages was markedly lower than those in M0 and M1 cells. HMOX1 gene expression levels were almost the same in all 3 subsets of macrophages even after oxLDL treatment. The present study demonstrated transcriptional alterations in polarized macrophages during oxLDL treatment. The data suggested that oxLDL uptake may affect TGF-β1- and NF-κB-mediated functions of M1 macrophages, but not those of M0 or M2 macrophages. It is likely that M1 macrophages characteristically respond to oxLDL.