IL-4-Primed Microglial Extracellular Vesicles Attenuate Rotenone-Induced Cell Death in SH-SY5Y Cells: A Contributory Role for miR-191-5p.

Authors

Kemal Ugur Tufekci, Burak I Arioz, Aysen Cotuk, Cagla Kiser, Bilgesu Ozturk, Tutku Yaras, Gokhan Karakulah, Pembe Keskinoglu, Alper Bagriyanik, Sermin Genc

Published in

ASN neuro. Volume 18. Issue 1. Pages 2712448. Epub Aug 07, 2026.

Abstract

Microglia contribute to central nervous system homeostasis and neuroprotection partly through the release of small extracellular vesicles (sEVs) carrying regulatory cargoes such as microRNAs. Interleukin-4 (IL-4) alters microglial state and secretory output; however, whether sEVs released from IL-4-treated microglia protect neurons against toxic injury, and which cargoes mediate these effects, remains unclear. Here, we investigated the protective effects of sEVs derived from the IL-4-treated HMC3 human microglial cell line in a rotenone-induced injury model in the SH-SY5Y cell line and examined the contribution of microRNA-191-5p to neuroprotection. Small RNA sequencing revealed a distinct miRNA profile in IL-4-sEVs, with microRNA-191-5p emerging as the most statistically significant upregulated candidate. Its enrichment was confirmed by RT-qPCR. PKH67-labeled sEV-associated fluorescence was detected in SH-SY5Y cells, indicating uptake of microglia-derived sEVs by recipient cells. Functionally, pretreatment with IL-4-sEVs significantly reduced rotenone-induced cell death and preserved cell morphology compared with untreated and control sEV-treated cells. To assess the contribution of microRNA-191-5p, IL-4-sEVs were loaded with a microRNA-191-5p antagomir, which reduced microRNA-191-5p levels and partially attenuated the protective effect of IL-4-sEVs. Together, these findings suggest that sEVs derived from the IL-4-treated HMC3 microglial cell line mitigate rotenone-induced injury in the SH-SY5Y cell line in vitro and that microRNA-191-5p contributes, at least in part, to this effect.

PMID:
42566293
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.

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