MicroRNA 21 Elicits a Pro-inflammatory Response in Macrophages, with Exosomes Functioning as Delivery Vehicles
MicroRNA 21 Elicits a Pro-inflammatory Response in Macrophages, with Exosomes Functioning as Delivery Vehicles
复制标题
MicroRNA21在巨噬细胞中引起促炎反应，外切体作为传递载体
DOI：
10.1007/s10753-021-01415-0
复制
发表时间：
2021-01-26
期刊：
影响因子：
5.1
通讯作者：
Nakajima, Yuichi
中科院分区：
文献类型：
--
作者：
Madhyastha, Radha;Madhyastha, Harishkumar;Nakajima, Yuichi
MicroRNAs可以通过调节巨噬细胞极化来调节炎症反应。尽管microRNA miR-21与炎症反应的关键过程有关，但其在巨噬细胞极化中的确切作用仍存在争议。在这项研究中，我们研究了内源性miRNA-21的功能相关性和外泌体的作用。转染miR-21质粒转染RAW 264.7巨噬细胞，通过流式细胞术、吞噬作用和实时PCR分析炎症细胞因子来评估炎症反应。为了了解信号通路的作用，我们用PI3K或NF κ b特异性抑制剂处理细胞，利用转染细胞的外泌体研究miR-21对幼稚巨噬细胞的旁分泌作用。miR-21的过表达导致促炎细胞因子的显著上调，推动细胞向促炎表型发展，部分参与PI3K和NF κ B信号通路。这些细胞还分泌富含miR-21的外泌体，这些外泌体在递送给幼稚巨噬细胞时，导致巨噬细胞表现出促炎活性。miR-21抑制剂的存在可以抑制炎症反应。本研究验证了miR-21具有促进炎症环境的倾向的促炎特性。我们的研究结果还强调了外泌体miR-21作为炎症条件下的生物标志物和治疗靶点的双重重要性。
MicroRNAs can regulate inflammatory responses by modulating macrophage polarization. Although microRNA miR-21 is linked to crucial processes involved in inflammatory responses, its precise role in macrophage polarization is controversial. In this study, we investigated the functional relevance of endogenous miRNA-21 and the role of exosomes. RAW 264.7 macrophages were transfected with miR-21 plasmid, and the inflammatory response was evaluated by flow cytometry, phagocytosis, and real-time PCR analysis of inflammatory cytokines. To understand the signaling pathways' role, the cells were treated with inhibitors specific for PI3K or NF kappa B. Exosomes from transfected cells were used to study the paracrine action of miR-21 on naive macrophages. Overexpression of miR-21 resulted in significant upregulation of pro-inflammatory cytokines, pushing the cells towards a pro-inflammatory phenotype, with partial involvement of PI3K and NF kappa B signal pathways. The cells also secreted miR-21 rich exosomes, which, on delivery to naive macrophages, caused them to exhibit pro-inflammatory activity. The presence of miR-21 inhibitor quenched the inflammatory response. This study validates the pro-inflammatory property of miR-21 with a tendency to foster an inflammatory milieu. Our findings also reinforce the dual importance of exosomal miR-21 as a biomarker and therapeutic target in inflammatory conditions.