Anada Natsuki, Nakayama Yoshinobu, Takeshita Jun, Kageyama Kyoko, Sakamoto Hiroatsu, Kamibayashi Takahiko, Nakajima Yasufumi
Anesthesiology and Intensive Care Medicine, Kansai Medical University, Hirakata, JPN.
Anesthesiology and Critical Care, Faculty of Medicine, Kindai University, Osakasayama, JPN.
Cureus. 2024 Jul 3;16(7):e63736. doi: 10.7759/cureus.63736. eCollection 2024 Jul.
Introduction The efficient clearance of bacteria by macrophages is crucial for the timely resolution of inflammation. In this study, we investigated the role of microRNA-21 (miR-21)-induced phagocytosis and its intracellular signaling pathways in human macrophages . Methods Human peripheral blood mononuclear cells (PBMCs) were isolated from whole blood collected from 15 healthy volunteers. Differentiated human macrophages were incubated with lipopolysaccharide (LPS) to determine the time course of changes in phagocytic activity and miR-21 expression. The expression of candidate genes targeted by miR-21 and its downstream effectors was quantitatively assessed. The effects of miR-21 modulation were also examined via transfection with miR-21 mimics and inhibitors. Results Incubation of human macrophages with LPS upregulated both phagocytosis and miR-21 expression. Notably, changing miR-21 expression levels using miR-21 mimics or inhibitors led to significant and opposite changes in the expression of its downstream effectors. miR-21 induction in macrophages downregulated PDCD4 and PTEN, promoted the phosphorylation of Akt and the production of the anti-inflammatory cytokine IL-10, and facilitated phagocytosis. Conclusion This study directly confirms that LPS upregulates macrophage phagocytosis and miR-21 expression. Elevated miR-21 levels in macrophages enhanced phagocytosis, contributing to an anti-inflammatory phenotype. These findings underscore the importance of miR-21 in resolving inflammation.
引言 巨噬细胞对细菌的有效清除对于炎症的及时消退至关重要。在本研究中，我们调查了微小RNA-21（miR-21）诱导的吞噬作用及其在人类巨噬细胞中的细胞内信号通路的作用。方法 从15名健康志愿者采集的全血中分离出人类外周血单核细胞（PBMC）。将分化的人类巨噬细胞与脂多糖（LPS）孵育，以确定吞噬活性和miR-21表达的时间变化过程。对miR-21靶向的候选基因及其下游效应物的表达进行定量评估。还通过转染miR-21模拟物和抑制剂来检测miR-21调节的作用。结果 用LPS孵育人巨噬细胞可上调吞噬作用和miR-21表达。值得注意的是，使用miR-21模拟物或抑制剂改变miR-21表达水平会导致其下游效应物的表达发生显著且相反的变化。巨噬细胞中miR-21的诱导下调了PDCD4和PTEN，促进了Akt的磷酸化和抗炎细胞因子IL-10的产生，并促进了吞噬作用。结论 本研究直接证实LPS上调巨噬细胞吞噬作用和miR-21表达。巨噬细胞中升高的miR-21水平增强了吞噬作用，促成了抗炎表型。这些发现强调了miR-21在炎症消退中的重要性。
