University Clinic and Outpatient Clinic for Anesthesiology and Operative Intensive Care, University Medicine Halle (Saale), Franzosenweg 1a, 06112 Halle (Saale), Germany.
Genes (Basel). 2022 Jan 24;13(2):211. doi: 10.3390/genes13020211.
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.
适当调节巨噬细胞极化对于机体的健康和病原体控制至关重要。分化控制已知发生在转录和转录后水平。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，以模拟炎症环境中 M1 样巨噬细胞的分化。我们发现革兰氏阳性刺激导致 miR-7a-5p、miR-148a-3p、miR-155-5p 和 miR-351-5p 的表达增加。值得注意的是，这些 miRNA 被发现靶向 Rac1-PI3K-Akt 途径和 MyD88 依赖性途径的抑制性介质。相比之下，革兰氏阴性刺激诱导的 miR-9-5p、miR-27b-3p、miR-93-5p 和 miR-106b-5p 的下调被认为靶向 Rac1-PI3K-Akt 途径和 MyD88 依赖性途径的关键成员。这些结果表明，TLR 诱导的巨噬细胞 miRNA 谱变化精细调节了巨噬细胞的极化。在这里，miRNA 介导的 M1 分化的启动似乎在革兰氏阳性和革兰氏阴性环境中在机制和涉及的 miRNA 方面有所不同。
