Exosomes from IL-1β-Primed Mesenchymal Stem Cells Inhibited IL-1β- and TNF-α-Mediated Inflammatory Responses in Osteoarthritic SW982 Cells
Exosomes from IL-1β-Primed Mesenchymal Stem Cells Inhibited IL-1β- and TNF-α-Mediated Inflammatory Responses in Osteoarthritic SW982 Cells
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DOI：
10.1007/s13770-020-00324-x
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发表时间：
2021-01-25
影响因子：
3.6
通讯作者：
Min, Byoung-Hyun
中科院分区：
文献类型：
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作者：
Kim, Mijin;Shin, Dong Il;Min, Byoung-Hyun
背景技术背景：来源于间充质干细胞（mesenchymal stem cells，MSCs）的外泌体对骨关节炎（osteoarthritis，OA）具有抗炎作用，但其生物学作用及机制尚不清楚。本研究探讨了IL-1 β致敏的MSC来源的exosomes（MSC-Exo）在骨关节炎SW982细胞中的抗炎作用及其机制。方法：用白细胞介素（IL）-1 β和肿瘤坏死因子（TNF）-α诱导SW982细胞OA表型。检查了没有引发的外泌体（MSC-Exo）或有IL-1 β引发的外泌体（MSC-IL-Exo）对促炎因子或抗炎因子表达的影响，并检查了SW 982细胞中I κ B α的量。用RNA酶处理外泌体以去除RNA。使用模拟物和抑制剂检查miR-147 b的作用。研究结果：MSC-IL-Exo对促炎细胞因子（IL-1 β、IL-6和单核细胞趋化蛋白-1）表达的抑制作用强于MSC-Exo。MSCs-IL-Exo可增强抗炎症因子SOCS3和SOCS6的表达。IL-1 β预处理可增加MSC-IL-Exo中RNA的含量，而RNase预处理则可抑制MSC-IL-Exo的抗炎作用。在MSC-IL-Exo中发现的miR-147 b的量远大于MSC-Exo。miR-147 b模拟物显著抑制炎性细胞因子的表达，而miR-147 b抑制剂仅部分阻断MSC-IL-Exo的抗炎作用。MSC-IL-Exo和miR-147 B模拟物可抑制IL-1 β和TNF-α对I κ B α（一种活化B细胞（NF-κ B）的核因子κ轻链增强子抑制剂）的减少。结论：该研究表明，具有IL-1 β引发的MSC外泌体在骨关节炎SW982细胞中表现出显著增强的抗炎活性。IL-1 β引发的MSC外泌体的作用由miRNA如miR-147 B介导，并涉及NF-κ B途径的抑制。
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.