BONE MARROW MESENCHYMAL STEM CELLS SUPPRESS ACUTE LUNG INJURY INDUCED BY LIPOPOLYSACCHARIDE THROUGH INHIBITING THE TLR2, 4/NF-κB PATHWAY IN RATS WITH MULTIPLE TRAUMA
BONE MARROW MESENCHYMAL STEM CELLS SUPPRESS ACUTE LUNG INJURY INDUCED BY LIPOPOLYSACCHARIDE THROUGH INHIBITING THE TLR2, 4/NF-κB PATHWAY IN RATS WITH MULTIPLE TRAUMA
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DOI：
10.1097/shk.0000000000000548
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发表时间：
2016-06-01
期刊：
影响因子：
3.1
通讯作者：
Pan, Jingye
中科院分区：
文献类型：
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作者：
Li, Dequan;Pan, Xuebo;Pan, Jingye
背景：多发伤常导致急性肺损伤(ALI)等多器官功能障碍综合征(MODS)。寻找治疗ALI的有效方法仍然是一个医学和社会经济挑战。多项研究表明，骨髓间充质干细胞(BMSCs)具有强大的抗炎活性，输注BMSCs可有效抑制炎症和自身免疫性疾病。方法：本研究通过研究TLR2、4/NF-kappaB信号通路，探讨骨髓间充质干细胞对内毒素诱导的急性肺损伤的治疗价值。为探讨骨髓间充质干细胞对多发伤大鼠的免疫抑制作用，用脂多糖诱导大鼠急性肺损伤后给予骨髓间充质干细胞治疗。肺组织学检查。分别于治疗后3、6、12、24 h检测血清促炎因子TNFα、IL-6、IL-1β及抗炎因子IL-10水平。同时检测肺组织中TLR2和TLR4的表达，以及肺组织中p65的磷酸化水平。结果：我们发现BMSCs减轻了炎症损伤，在mRNA和蛋白水平上抑制了脂多糖诱导的TLR2和TLR4的表达，并抑制了p65的磷酸化。此外，骨髓间充质干细胞的输注还下调了促炎性肿瘤坏死因子α、IL-6和IL-1β的丰度，上调了抗炎IL-10的丰度。结论：骨髓间充质干细胞通过抑制TLR2、4介导的核因子-kappaB信号通路抑制炎症反应，提示骨髓间充质干细胞可用于多发伤后ALI的治疗。
Background: Multiple trauma normally leads to acute lung injury (ALI) and other multiple organ dysfunction syndrome (MODS). Finding effective treatments for ALI remains a medical as well as socioeconomic challenge. Several studies show that bone marrow mesenchymal stem cells (BMSCs) have the potent anti-inflammation activity and transfusion of BMSCs can effectively inhibit inflammatory and autoimmune diseases. Methods: In this study, we investigated the TLR2, 4/NF-kappa B signaling pathway to determine the therapeutic value of BMSCs on lipopolysaccharide (LPS)-induced ALI. To investigate the immunosuppression effects of BMSCs, rats subjected to multiple trauma were administrated with LPS to induce ALI and then treated with BMSCs. The histology of the lung was examined. Serum levels of the pro-inflammatory factors TNF alpha, interleukin (IL)-6, and IL-1 beta, as well as anti-inflammatory factor IL-10 were measured at 3, 6, 12, and 24 h after the treatment. Moreover, expressions of TLR2 and TLR4 at the mRNA and protein levels, as well as phosphorylation of p65 in the lungs, were assessed at these time points. Results: We found that BMSCs reduced inflammatory injury, inhibited LPS-induced upregulation of TLR2 and TLR4 expression at the mRNA and protein levels, and compromised p65 phosphorylation. In addition, infusion of BMSCs also downregulated the abundance of pro-inflammatory TNF alpha, IL-6, and IL-1 beta and upregulated the abundance of anti-inflammatory IL-10 levels in the serum. Conclusions: Our results suggest that BMSCs suppress the inflammatory reactions through inhibition of the TLR2, 4 mediated NF-kappa B signal pathway, which hints that BMSCs can potentially be used to treat ALI in multiple trauma.