Mesenchymal stem cells inhibit lipopolysaccharide-induced inflammatory responses of BV2 microglial cells through TSG-6.
Mesenchymal stem cells inhibit lipopolysaccharide-induced inflammatory responses of BV2 microglial cells through TSG-6.
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DOI：
10.1186/1742-2094-11-135
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发表时间：
2014-08-04
影响因子：
9.3
通讯作者：
Jiang X
中科院分区：
文献类型：
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作者：
Liu Y;Zhang R;Yan K;Chen F;Huang W;Lv B;Sun C;Xu L;Li F;Jiang X
小胶质细胞是脑组织中主要的免疫活性细胞，小胶质细胞介导的炎症与各种神经元疾病的发病机制有关。最近，许多研究表明间充质干细胞（MSC）表现出卓越的能力，通过释放多种生物活性分子来调节炎症和免疫反应，从而保护中枢神经系统。此前，我们报道间充质干细胞具有调节创伤性脑损伤模型中炎症反应的能力，其潜在机制可能部分归因于上调的TNF-α刺激的基因/蛋白6（TSG-6）表达。然而，TSG-6是否通过影响小胶质细胞发挥抗炎作用尚不完全清楚。在这项研究中，我们研究了 MSC 和 TSG-6 在体外脂多糖 (LPS) 诱导的 BV2 小胶质细胞激活模型中的抗炎作用。我们发现 MSC 和 TSG-6 显着抑制激活的小胶质细胞中促炎介质的表达。然而，当 TSG-6 表达被沉默时，MSC 对小胶质细胞的影响就会减弱。此外，我们发现LPS刺激的BV2小胶质细胞中核因子（NF）-κB和丝裂原激活蛋白激酶（MAPK）通路的激活被TSG-6显着抑制。此外，我们发现 BV2 小胶质细胞中 CD44 的存在对于 MSC 和 TSG-6 介导的 BV2 小胶质细胞中促炎基因表达以及 NF-κB 和 MAPK 激活的抑制至关重要。这项研究的结果表明，间充质干细胞可以通过 TSG-6 调节小胶质细胞的活化，并且 TSG-6 可以减弱活化小胶质细胞中的炎症级联反应。我们的研究表明，新的机制导致 MSC 对小胶质细胞的免疫调节作用，并且 MSC 以及 TSG-6 可能是治疗与小胶质细胞活化相关的神经创伤性损伤或神经炎症性疾病的有前途的治疗剂。
Microglia are the primary immunocompetent cells in brain tissue and microglia-mediated inflammation is associated with the pathogenesis of various neuronal disorders. Recently, many studies have shown that mesenchymal stem cells (MSCs) display a remarkable ability to modulate inflammatory and immune responses through the release of a variety of bioactive molecules, thereby protecting the central nervous system. Previously, we reported that MSCs have the ability to modulate inflammatory responses in a traumatic brain injury model and that the potential mechanisms may be partially attributed to upregulated TNF-α stimulated gene/protein 6 (TSG-6) expression. However, whether TSG-6 exerts an anti-inflammatory effect by affecting microglia is not fully understood. In this study, we investigated the anti-inflammatory effects of MSCs and TSG-6 in an in vitro lipopolysaccharide (LPS)-induced BV2 microglial activation model. We found that MSCs and TSG-6 significantly inhibited the expression of pro-inflammatory mediators in activated microglia. However, MSC effects on microglia were attenuated when TSG-6 expression was silenced. In addition, we found that the activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) pathways in LPS-stimulated BV2 microglial cells was significantly inhibited by TSG-6. Furthermore, we found that the presence of CD44 in BV2 microglial cells was essential for MSC- and TSG-6-mediated inhibition of pro-inflammatory gene expression and of NF-κB and MAPK activation in BV2 microglial cells. The results of this study suggest that MSCs can modulate microglia activation through TSG-6 and that TSG-6 attenuates the inflammatory cascade in activated microglia. Our study indicates that novel mechanisms are responsible for the immunomodulatory effect of MSCs on microglia and that MSCs, as well as TSG-6, might be promising therapeutic agents for the treatment of neurotraumatic injuries or neuroinflammatory diseases associated with microglial activation.
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