Related Experiment Video
Updated: Jun 16, 2026
Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
IL-6-Mediated Upregulated miRNAs in Extracellular Vesicles Derived from Lund Human Mesencephalic (LUHMES) Cells:
Kento Nishi1,2, Hiroto Izumi1,3, Taisuke Tomonaga3
1Center for Stress-Related Disease Control and Prevention, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
Abstract:
Psychological stress plays a major role in depression, and interleukin-6 (IL-6) is elevated during depression and psychological stress. MicroRNAs (miRNAs) in extracellular vesicles (EVs), including exosomes and microvesicles, suppress mRNA expression in other cells when endocytosed. In this study, we analyzed the effect of IL-6 on EVs secreted by neural precursor cells. Cells from the human immortalized neural precursor cell line LUHMES were treated with IL-6. EVs were collected using a nanofiltration method. We then analyzed the uptake of LUHMES-derived EVs by astrocytes (ACs) and microglia (MG). Microarray analysis of miRNAs was performed using EV-incorporated RNA and intracellular RNA from ACs and MG to search for increased numbers of miRNAs. We applied the miRNAs to ACs and MG, and examined the cells for suppressed mRNAs. IL-6 increased several miRNAs in the EVs. Three of these miRNAs were originally low in ACs and MG (hsa-miR-135a-3p, hsa-miR-6790-3p, and hsa-miR-11399). In ACs and MG, hsa-miR-6790-3p and hsa-miR-11399 suppressed four mRNAs involved in nerve regeneration (NREP, KCTD12, LLPH, and CTNND1). IL-6 altered the types of miRNAs in EVs derived from neural precursor cells, by which mRNAs involved in nerve regeneration were decreased in ACs and MG. These findings provide new insights into the involvement of IL-6 in stress and depression.
Insights
Interleukin-6 (IL-6) alters microRNAs (miRNAs) in extracellular vesicles from neural cells, impacting nerve regeneration in astrocytes and microglia. This suggests a novel mechanism linking IL-6, stress, and depression.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Psychological stress and elevated interleukin-6 (IL-6) are linked to depression.
- MicroRNAs (miRNAs) within extracellular vesicles (EVs) regulate gene expression in recipient cells.
Purpose of the Study:
- To investigate the impact of IL-6 on EVs secreted by neural precursor cells.
- To determine how IL-6-modulated EVs affect astrocytes (ACs) and microglia (MG).
Main Methods:
- LUHMES neural precursor cells were treated with IL-6, and secreted EVs were isolated.
- EV uptake by ACs and MG was analyzed, followed by miRNA and mRNA profiling.
- The functional effects of specific miRNAs on target mRNAs in ACs and MG were assessed.
Main Results:
- IL-6 treatment increased specific miRNAs within neural precursor cell-derived EVs.
- Three miRNAs (hsa-miR-135a-3p, hsa-miR-6790-3p, hsa-miR-11399) were found to be upregulated in EVs.
- Two of these miRNAs (hsa-miR-6790-3p, hsa-miR-11399) suppressed mRNAs crucial for nerve regeneration (NREP, KCTD12, LLPH, CTNND1) in ACs and MG.
Conclusions:
- IL-6 modifies the miRNA cargo of EVs released by neural precursor cells.
- This alteration leads to the downregulation of nerve regeneration-associated mRNAs in astrocytes and microglia.
- The findings elucidate a potential molecular pathway connecting IL-6, stress, depression, and impaired nerve regeneration.
