Inflammation-induced cell-secreted migrasome promotes IL-6 expression in the recipient cells

Enhanced NF-κB signaling is critical for inflammatory disease development. The IL-6 amplifier, a hyper-induction machinery of NF-κB activation in non-immune cells, plays an important role in the local expression of inflammatory factors, including IL-6 cytokine, and their subsequent development. In this study, we demonstrated the transduction of IL-6 amplifiers via migrasomes, extracellular vesicles secreted by migrating cells. Migrasomes derived from IL-6 amplifier-induced human neuroglioma, H4 cells, were shown to promote inflammatory responses in the recipient cells. To conduct these experiments under controlled in vitro conditions, where the effects of secreted molecules in the surrounding environment are minimized, we employed a peptide-modified substrate that captures intact migrasomes. Remarkably, when migrasomes from the IL-6-amplifier-induced cells captured on a peptide-modified substrate were used to stimulate cells, even a small number of migrasomes was sufficient to induce IL-6 expression. These findings suggest that migrasomes contribute to inflammatory signaling via cell-to-cell communication, highlighting their potential roles in cytokine transduction and offering insights into therapeutic strategies targeting intercellular communication in inflammatory diseases.