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Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
MiR-146a-5p-enriched exosomes inhibit M1 macrophage activation and inflammatory response by targeting CD80
Han Zhang1,2, Yifen Wang1,3, Keqing Feng4
1Department of Infectious Diseases, Qingdao Municipal Hospital, Qingdao University, 5 Donghaizhong Road, Qingdao, Shandong Province, 266071, China.
Background:
Previous studies have demonstrated that miR-146a-5p negatively regulated the intrinsic immune and inflammatory responses, whether the miR-146a-5p-enriched exosomes possess the anti-inflammation effect remains unclear. This study aimed to investigate the effect of miR-146a-5p-enriched exosomes on M1 macrophage activation and inflammatory response and the potential molecular mechanism.
Methods:
GEO database was used to analyze the expression of miR-146a-5p in serum exosomes of MASH patients. MiR-146a-5p levels in primary hepatocytes, macrophages, and serum exosomes of MASH mice were measured. MiR-146a-5p-enriched exosomes were constructed and the effects on M1 macrophages activation and inflammatory factors release were investigated. The target gene of miR-146a-5p was predicted and verified.
Results:
Serum exosomal miR-146a-5p level was decreased in MASH patients analyzed by GEO database. The miR-146a-5p levels in primary cultured hepatocytes and macrophages of MASH mice were decreased. Serum exosomal miR-146a-5p level was decreased and negatively correlated with the concentrations of IL-6 in MASH mice. Furthermore, miR-146a-5p-enriched exosomes inhibited the M1 macrophages activation and the expression of pro-inflammatory factors MCP-1, IL-6, and TNF-α. CD80 was predicted as the potential target gene of miR-146a-5p, and the expression of CD80 was regulated by miR-146a-5p. In addition, the inhibitory effect of miR-146a-5p on M1 macrophages activation and inflammatory factors release was restored when CD80 was over-expressed.
Conclusions:
This study demonstrated that miR-146a-5p-enriched exosomes can inhibit the M1 macrophages activation and reduce the release of pro-inflammatory factors by targeting CD80.
Insights
MicroRNA-146a-5p (miR-146a-5p)-enriched exosomes reduce inflammation by inhibiting M1 macrophage activation. This effect is mediated by targeting CD80, offering a potential therapeutic strategy for inflammatory conditions.
Area of Science:
- Immunology
- Molecular Biology
- Exosome Biology
Background:
- MicroRNA-146a-5p (miR-146a-5p) is known to regulate immune responses.
- The anti-inflammatory potential of miR-146a-5p-enriched exosomes remains largely unexplored.
- This study investigates the role of miR-146a-5p-enriched exosomes in modulating M1 macrophage activation and inflammation.
Purpose of the Study:
- To determine the effect of miR-146a-5p-enriched exosomes on M1 macrophage activation.
- To elucidate the molecular mechanism underlying the anti-inflammatory action of miR-146a-5p-enriched exosomes.
- To assess the therapeutic potential of miR-146a-5p-enriched exosomes in inflammatory diseases.
Main Methods:
- Analysis of serum exosomal miR-146a-5p levels in MASH patients and mice using GEO database and quantitative measurements.
- Construction and characterization of miR-146a-5p-enriched exosomes.
- In vitro assessment of exosome effects on M1 macrophage activation and inflammatory cytokine release.
- Prediction and experimental validation of miR-146a-5p target genes.
Main Results:
- Serum exosomal miR-146a-5p levels were decreased in MASH patients and mice, correlating negatively with IL-6.
- miR-146a-5p-enriched exosomes significantly inhibited M1 macrophage activation and the release of pro-inflammatory factors (MCP-1, IL-6, TNF-α).
- CD80 was identified as a direct target of miR-146a-5p, and its overexpression reversed the inhibitory effects of miR-146a-5p on M1 macrophages.
Conclusions:
- miR-146a-5p-enriched exosomes exert anti-inflammatory effects by suppressing M1 macrophage activation.
- The mechanism involves the direct targeting of CD80 by miR-146a-5p.
- These findings highlight the therapeutic potential of miR-146a-5p-enriched exosomes in managing inflammatory conditions.
