miRNA-Mediated Priming of Macrophage M1 Differentiation Differs in Gram-Positive and Gram-Negative Settings.

miRNA-Mediated Priming of Macrophage M1 Differentiation Differs in Gram-Positive and Gram-Negative Settings.
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DOI:
10.3390/genes13020211
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发表时间:
2022-01-24
期刊:
影响因子:
3.5
通讯作者:
Schumann J
Schumann J
中科院分区:
生物学3区
文献类型:
--
作者:
Riechert G;Maucher D;Schmidt B;Schumann J

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巨噬细胞极化的适当调节对于生物体的健康和病原体控制是必不可少的。已知分化控制发生在转录水平以及转录后水平。然而,所涉及的机制尚未完全阐明。在这项研究中,我们将巨噬细胞与活的革兰氏阳性和革兰氏阴性细菌共培养,以模拟巨噬细胞在炎症环境中分化为M1样类型。我们发现革兰氏阳性刺激导致miR-7a-5 p、miR-148 a-3 p、miR-155- 5 p和miR-351- 5 p的表达增加。值得注意的是,这些miRNAs被发现靶向Rac 1-PI 3 K-Akt途径和MyD 88依赖性途径的抑制性介体。相比之下,已知革兰氏阴性刺激诱导的miR-9- 5 p、miR-27 b-3 p、miR-93- 5 p和miR-106 b-5 p下调靶向Rac 1-PI 3 K-Akt通路和MyD 88依赖性通路的关键成员。这些结果结合在一起,指出TLR诱导的巨噬细胞miRNA谱变化对巨噬细胞极化的微调。在此,miRNA介导的M1分化启动在革兰氏阳性和革兰氏阴性环境中似乎在机制和所涉及的miRNA方面有所不同。
A proper regulation of macrophage polarization is essential for the organism’s health and pathogen control. Differentiation control is known to occur at the transcriptional as well as the posttranscriptional levels. The mechanisms involved, however, have not yet been fully elucidated. In this study, we co-cultured macrophages with viable Gram-positive and Gram-negative bacteria to mimic macrophage differentiation to the M1-like type in an inflammatory milieu. We found that Gram-positive stimulation resulted in increased expressions of miR-7a-5p, miR-148a-3p, miR-155-5p, and miR-351-5p. Of note, these miRNAs were found to target inhibitory mediators of the Rac1-PI3K-Akt pathway and the MyD88-dependent pathway. In contrast, Gram-negative stimulation-induced downregulation of miR-9-5p, miR-27b-3p, miR-93-5p, and miR-106b-5p is known to target key members of the Rac1-PI3K-Akt pathway and the MyD88-dependent pathway. These results, taken together, point to a fine-tuning of macrophage polarization by TLR-induced changes in macrophage miRNA profiles. Here, the miRNA-mediated priming of M1 differentiation seems to differ in the Gram-positive and Gram-negative settings in terms of the mechanism and miRNAs involved.
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