MicroRNA let-7c regulates macrophage polarization.

MicroRNA let-7c regulates macrophage polarization.
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DOI:
10.4049/jimmunol.1202496
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发表时间:
2013-06-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Liu G
Liu G
中科院分区:
其他
文献类型:
--
作者:
Banerjee S;Xie N;Cui H;Tan Z;Yang S;Icyuz M;Abraham E;Liu G

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巨噬细胞表现出高水平的可塑性,具有在M1和M2极化表型之间进行动态转变的能力。miRNAs在调节巨噬细胞极化中的作用在很大程度上尚未确定。在这项研究中,我们发现microRNA let-7 c在M-BMM(M2巨噬细胞)中的表达水平高于GM-BMM(M1巨噬细胞)。与来自正常肺的肺泡巨噬细胞相比,来自纤维化肺的肺泡巨噬细胞中的let-7 c水平也更高。let-7 c在M-BMM向GM-BMM转化时表达降低,而在GM-BMM向M-BMM转化时表达升高。LPS刺激降低了M-BMM中let-7 c的表达。我们发现let-7 c在GM-BMM中的过表达减少了M1表型表达,同时促进了向M2表型的极化。相反,在M-BMM中敲低let-7 c促进M1极化,并减少M2表型表达。我们发现let-7 c靶向C/EBP-δ,这是一种在炎症反应中起重要作用的转录因子。此外,我们发现let-7 c调节巨噬细胞的杀菌和吞噬活性,这两种功能表型与巨噬细胞极化有关。我们的数据表明microRNA let-7 c在调节巨噬细胞极化中起重要作用。
Macrophages demonstrate a high level of plasticity, with the ability to undergo dynamic transition between M1 and M2 polarized phenotypes. The role of miRNAs in regulating macrophage polarization has been largely undefined. In this study, we found that microRNA let-7c is expressed at a higher level in M-BMM (M2 macrophages) than in GM-BMM (M1 macrophages). let-7c levels are also greater in alveolar macrophages from fibrotic lungs as compared to those from normal lungs. let-7c expression was decreased when M-BMM converted to GM-BMM whereas increased when GM-BMM converted to M-BMM. LPS stimulation reduced let-7c expression in M-BMM. We found that overexpression of let-7c in GM-BMM diminished M1 phenotype expression while promoting polarization to the M2 phenotype. In contrast, knockdown of let-7c in M-BMM promoted M1 polarization, and diminished M2 phenotype expression. We found that let-7c targets C/EBP-δ, a transcriptional factor that plays an important role in inflammatory response. Furthermore, we found that let-7c regulates bactericidal and phagocytic activities of macrophages, two functional phenotypes implicated in macrophage polarization. Our data suggest that the microRNA let-7c plays an important role in regulating macrophage polarization.
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