Exosomes from IL-1β-Primed Mesenchymal Stem Cells Inhibited IL-1β- and TNF-α-Mediated Inflammatory Responses in Osteoarthritic SW982 Cells

BACKGROUND: Exosomes from mesenchymal stem cells (MSCs) show anti-inflammatory effect on osteoarthritis (OA); however, their biological effect and mechanism are not yet clearly understood. This study investigated the anti-inflammatory effect and mechanism of MSC-derived exosomes (MSC-Exo) primed with IL-1 beta in osteoarthritic SW982 cells. METHODS: SW982 cells were treated with interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha to induce the OA phenotype. The effect of exosomes without priming (MSC-Exo) or with IL-1 beta priming (MSC-IL-Exo) was examined on the expression of pro- or anti-inflammatory factors, and the amount of I kappa B alpha was examined in SW982 cells. Exosomes were treated with RNase to remove RNA. The role of miR-147b was examined using a mimic and an inhibitor. RESULTS: MSC-IL-Exo showed stronger inhibitory effects on the expression of pro-inflammatory cytokines (IL-1 beta, IL-6, and monocyte chemoattractant protein-1) than MSC-Exo. The expression of anti-inflammatory factors (SOCS3 and SOCS6) was enhanced by MSCs-IL-Exo. Priming with IL-1 beta increased RNA content in MSC-IL-Exo, and pretreatment with RNase abolished anti-inflammatory effect in SW982 cells. miR-147b was found in much larger amounts in MSC-IL-Exo than in MSC-Exo. The miR-147b mimic significantly inhibited the expression of inflammatory cytokines, while the miR-147b inhibitor only partially blocked the anti-inflammatory effect of MSC-IL-Exo. MSC-IL-Exo and miR-147b mimic inhibited the reduction of I kappa B alpha, an nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) inhibitor, by IL-1 beta and TNF-alpha. CONCLUSION: This study showed that MSC exosomes with IL-1 beta priming exhibit significantly enhanced anti-inflammatory activity in osteoarthritic SW982 cells. The effect of IL-1 beta-primed MSC exosomes is mediated by miRNAs such as miR-147b and involves inhibition of the NF-kappa B pathway.

Automated summary

The study showed that MSC exosomes primed with IL-1 beta exhibit significantly enhanced anti-inflammatory activity in osteoarthritic SW982 cells. This effect is mediated by miRNAs such as miR-147b and involves inhibition of the NF-kappa B pathway. Additionally, the presence of miR-147b in MSC-IL-Exo plays a crucial role in the regulation of inflammatory cytokines.