miR-195 inhibits macrophages pro-inflammatory profile and impacts the crosstalk with smooth muscle cells.
miR-195 inhibits macrophages pro-inflammatory profile and impacts the crosstalk with smooth muscle cells.
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DOI：
10.1371/journal.pone.0188530
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Almeida MI
中科院分区：
文献类型：
--
作者：
Bras JP;Silva AM;Calin GA;Barbosa MA;Santos SG;Almeida MI
巨噬细胞是动脉粥样硬化斑块的主要成分。最近的研究表明，促炎性M1巨噬细胞是促动脉粥样硬化的，而M2巨噬细胞促进斑块稳定性。此外，Toll样受体信号通路与动脉粥样硬化斑块的形成、演变和消退有关。我们建议microRNA作为这些过程的关键调节因子。在这种情况下，我们的目标是使用miR-195促进炎症消退，以减少M1样巨噬细胞极化，并评估这种作用的分子机制，以及探索平滑肌细胞募集的功能后果。从外周血单核细胞分化人原代巨噬细胞，并用LPS或IL-10刺激以分别促进M1或M2 c极化。与M1巨噬细胞相比，M2 c巨噬细胞中miR-195水平上调。在用LPS和IFN-γ刺激的THP-1巨噬细胞中，结果显示与乱序对照相比，miR-195过表达降低了TLR 2水平。此外，M1刺激后，巨噬细胞中p54 JNK、p46 JNK和p38 MAPK的磷酸化形式被miR-195降低。此外，miR-195显著降低了M1刺激的巨噬细胞培养物上清液中IL-1β、IL-6和TNF-α促炎细胞因子的水平。在功能水平上，平滑肌细胞募集和迁移模型的结果表明，miR-195损害了M1巨噬细胞促进平滑肌细胞迁移的能力。总之，miR-195参与巨噬细胞极化并抑制TLR 2炎症通路介质。此外，miR-195削弱了巨噬细胞对平滑肌细胞募集能力和迁移特征的影响。因此，miR-195可能被用作一种新的潜在的工具，以促进炎症的解决，在心血管研究。
Macrophages are a main component of atherosclerotic plaques. Recent studies suggest that pro-inflammatory M1 macrophages are pro-atherogenic while M2 macrophages promote plaque stability. Moreover, toll-like receptor signalling pathways are implicated in atherosclerotic plaque formation, evolution and regression. We propose microRNAs as key regulators of these processes. In this context, our goal is to promote inflammation resolution using miR-195 to reduce M1-like macrophage polarization and to evaluate the molecular mechanisms underlying such effect, as well as to explore the functional consequences for smooth muscle cell recruitment. Human primary macrophages were differentiated from peripheral blood monocytes and stimulated with LPS or IL-10 to promote M1 or M2c polarization, respectively. miR-195 levels were upregulated in M2c macrophages compared with M1 macrophages. In THP-1 macrophages stimulated with LPS and IFN-γ, results show that TLR2 levels were reduced by miR-195 overexpression compared with scrambled control. In addition, phosphorylated forms of p54 JNK, p46 JNK and p38 MAPK were decreased by miR-195 in macrophages following M1 stimulation. Moreover, miR-195 significantly decreased levels of IL-1β, IL-6 and TNF-α pro-inflammatory cytokines in the supernatants of M1-stimulated macrophage cultures. At the functional level, results from smooth muscle cell recruitment and migration models showed that miR-195 impairs the capacity of M1 macrophages to promote smooth muscle cells migration. In conclusion, miR-195 is involved in macrophage polarization and inhibits TLR2 inflammatory pathway mediators. Moreover, miR-195 impairs the effect of macrophages on smooth muscle cells recruitment capacity and migration profile. Thus, miR-195 might be used as a new potential tool to promote inflammation resolution in cardiovascular research.
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影响因子：
4.6
作者：
Burdon KP;Rudock ME;Lehtinen AB;Langefeld CD;Bowden DW;Register TC;Liu Y;Freedman BI;Carr JJ;Hedrick CC;Rich SS
通讯作者：
Rich SS
影响因子：
2.2
作者：
Mazza, G.;Rossmanith, E.;Pfeiffer, D.
通讯作者：
Pfeiffer, D.
DOI：
10.1038/nri3520
发表时间：
2013-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
15.9
作者：
Mullick, AE;Tobias, PS;Curtiss, LK
通讯作者：
Curtiss, LK
影响因子：
4.8
作者：
Banerjee, Sami;Cui, Huachun;Liu, Gang
通讯作者：
Liu, Gang