Transcriptomic analysis of human polarized macrophages: more than one role of alternative activation?
Transcriptomic analysis of human polarized macrophages: more than one role of alternative activation?
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DOI：
10.1371/journal.pone.0119751
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Bonadonna RC
中科院分区：
文献类型：
--
作者：
Derlindati E;Dei Cas A;Montanini B;Spigoni V;Curella V;Aldigeri R;Ardigò D;Zavaroni I;Bonadonna RC
巨噬细胞是一种异质细胞群，在细胞因子环境极化的反应中，经典活化的巨噬细胞（M1）或选择性活化的巨噬细胞（M2）。这种可塑性使得巨噬细胞在调节炎症、免疫反应和组织重塑中至关重要，并成为动脉粥样硬化等炎症性疾病的新治疗靶点。本研究的目的是描述不同极化的人巨噬细胞的转录组谱，对不同巨噬细胞亚型的生物学功能提出新的假设。体外用IFN-γ和LPS （M1）、IL-4 （M2a）和IL-10 （M2c）诱导献血者循环单核/巨噬细胞极化。未刺激细胞（RM）作为时间对照。利用全基因组安捷伦微阵列技术在极化后6、12和24小时检测M1、M2a、M2c和RM的基因表达谱。与RM相比，M1显著上调了与免疫和炎症相关的通路，而M2a则相反。相反，在M1和M2a中分别观察到线粒体代谢表达的减少和增加，与胰岛素抵抗和胰岛素敏感模式一致。一些通路表达的时间顺序似乎与M1函数有一定的相关性。最后，与RM相比，M2a中促进炎症和组织重塑的典型和非典型Wnt基因和基因组上调。我们的数据在体外极化人巨噬细胞：1。确认和扩展已知的炎症和抗炎基因表达模式；2. 线粒体代谢的变化分别与M1和M2a的胰岛素抵抗和胰岛素敏感性相关；3. 强调基因表达时间在M1功能中的潜在相关性；4. 揭示Wnt通路在M2a中的增强表达，提示M2a在炎症性疾病中可能具有双重（促炎和抗炎）作用。
Macrophages are a heterogeneous cell population which in response to the cytokine milieu polarize in either classically activated macrophages (M1) or alternatively activated macrophages (M2). This plasticity makes macrophages essential in regulating inflammation, immune response and tissue remodeling and a novel therapeutic target in inflammatory diseases such as atherosclerosis. The aim of the study was to describe the transcriptomic profiles of differently polarized human macrophages to generate new hypotheses on the biological function of the different macrophage subtypes. Polarization of circulating monocytes/macrophages of blood donors was induced in vitro by IFN-γ and LPS (M1), by IL-4 (M2a), and by IL-10 (M2c). Unstimulated cells (RM) served as time controls. Gene expression profile of M1, M2a, M2c and RM was assessed at 6, 12 and 24h after polarization with Whole Human Genome Agilent Microarray technique. When compared to RM, M1 significantly upregulated pathways involved in immunity and inflammation, whereas M2a did the opposite. Conversely, decreased and increased expression of mitochondrial metabolism, consistent with insulin resistant and insulin sensitive patterns, was seen in M1 and M2a, respectively. The time sequence in the expression of some pathways appeared to have some specific bearing on M1 function. Finally, canonical and non-canonical Wnt genes and gene groups, promoting inflammation and tissue remodeling, were upregulated in M2a compared to RM. Our data in in vitro polarized human macrophages: 1. confirm and extend known inflammatory and anti-inflammatory gene expression patterns; 2. demonstrate changes in mitochondrial metabolism associated to insulin resistance and insulin sensitivity in M1 and M2a, respectively; 3. highlight the potential relevance of gene expression timing in M1 function; 4. unveil enhanced expression of Wnt pathways in M2a suggesting a potential dual (pro-inflammatory and anti-inflammatory) role of M2a in inflammatory diseases.
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影响因子：
4.4
作者：
Bergenfelz, Caroline;Medrek, Catharina;Leandersson, Karin
通讯作者：
Leandersson, Karin
影响因子：
3.7
作者：
Cosín-Roger J;Ortiz-Masiá D;Calatayud S;Hernández C;Alvarez A;Hinojosa J;Esplugues JV;Barrachina MD
通讯作者：
Barrachina MD
DOI：
10.1016/j.bbrc.2005.03.007
发表时间：
2005-05-06
影响因子：
3.1
作者：
Kanazawa, A;Tsukada, S;Maeda, S
通讯作者：
Maeda, S
影响因子：
29
作者：
Bouhlel, M. Amine;Derudas, Bruno;Chinetti-Gbaguidi, Giulia
通讯作者：
Chinetti-Gbaguidi, Giulia
影响因子：
3.7
作者：
Liang H;Hussey SE;Sanchez-Avila A;Tantiwong P;Musi N
通讯作者：
Musi N