RRC ID 63637
著者 Madhyastha R, Madhyastha H, Nurrahmah QI, Purbasari B, Maruyama M, Nakajima Y.
タイトル MicroRNA 21 Elicits a Pro-inflammatory Response in Macrophages, with Exosomes Functioning as Delivery Vehicles.
ジャーナル Inflammation
Abstract 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 NFĸB. 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 NFĸB 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.
巻・号 44(4)
ページ 1274-1287
公開日 2021-8-1
DOI 10.1007/s10753-021-01415-0
PII 10.1007/s10753-021-01415-0
PMID 33501624
MeSH Animals Cell Communication / physiology* Cell Polarity / physiology Exosomes / metabolism* Exosomes / pathology Inflammation Mediators / metabolism* Macrophages / metabolism* Macrophages / pathology Mice MicroRNAs / metabolism* Phagocytosis / physiology RAW 264.7 Cells
IF 3.212
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)