骨髓间充质干细胞通过促进RvE1/ProD1和调节Treg/Th17平衡减轻脂多糖诱导的小鼠急性肺损伤。
Bone marrow mesenchymal stem cells attenuate LPS-induced acute lung injury in mice by promoting RvE1/ProD1 and modulating Treg/Th17 balance.
作者信息
Qian He-Bu, Zou Guijuan, Li Chao, He Qi-Fang, Liu Jun
机构信息
Department of Critical Care Medicine, Suzhou Ninth People's Hospital, The Affiliated Wujiang Hospital of Nantong University, Suzhou, China.
Gusu School of Nanjing Medical University, Department of Critical Care Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou Clinical Medical Center of Critical Care Medicine, Suzhou, China.
出版信息
Turk J Biol. 2021 Dec 20;46(2):173-185. doi: 10.3906/biy-2107-83. eCollection 2022.
Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are respiratory failures caused by excessive alveolar inflammation with high mortality. In this study, we investigated the effects of bone marrow mesenchymal stem cells (BMSCs) on lung injury of lipopolysaccharide (LPS)-induced ALI and explored the associated mechanisms. BMSCs were isolated, cultured, identified by staining with CD34 and CD44 surface markers. LPS-induced ALI mouse model was generated by injecting with LPS and divided into ALI group and ALI+BMSCs group. Mice treated without any reagents were assigned as Control, mice transplanted with BMSCs were assigned as BMSCs group. Regulatory T (Treg) and Th17 percentages were evaluated using flow cytometry. Proresolving mediators (resolvin E1 (RvE1), protectin D1 (ProD1)) in lung tissue and cytokines (interleukin-6 (IL-6) and IL-17) in serum were analyzed by ELISA. Myeloperoxidase (MPO) activity was determined. Cultured cells demonstrated typical characteristics of BMSCs. BMSCs transplantation (ALI+BMSCs) obviously alleviated LPS-induced ALI in mice. BMSCs transplantation significantly decreased MPO activity in LPS-induced ALI in mice compared to the Control group (p < 0.05). BMSCs transplantation markedly increased Treg percentages and decreased dendritic cells (DCs) and Th17 cells percentages compared to those of the Control group (p < 0.05). BMSCs transplantation remarkably enhanced RvE1 and ProD1 levels in LPS-induced ALI (ALI+BMSCs) compared to the ALI group (p < 0.05). BMSCs transplantation significantly attenuated IL-6 and IL-17 levels in serum of mice treated with LPS (ALI+BMSCs) compared to those of the ALI group (p < 0.05). In conclusion, BMSCs transplantation effectively attenuated LPS-induced pathological injury of ALI in mice, at least partly through promoting proresolving mediators RvE1 and ProD1 and modulating the balance of Treg/Th17.
急性肺损伤（ALI）及其严重形式急性呼吸窘迫综合征（ARDS）是由过度的肺泡炎症引起的呼吸衰竭，死亡率很高。在本研究中，我们研究了骨髓间充质干细胞（BMSCs）对脂多糖（LPS）诱导的ALI肺损伤的影响，并探讨了相关机制。分离、培养BMSCs，通过CD34和CD44表面标志物染色进行鉴定。通过注射LPS建立LPS诱导的ALI小鼠模型，并分为ALI组和ALI+BMSCs组。未用任何试剂处理的小鼠作为对照组，移植BMSCs的小鼠作为BMSCs组。使用流式细胞术评估调节性T（Treg）和Th17细胞百分比。通过ELISA分析肺组织中的促消退介质（消退素E1（RvE1）、保护素D1（ProD1））和血清中的细胞因子（白细胞介素-6（IL-6）和IL-17）。测定髓过氧化物酶（MPO）活性。培养的细胞表现出BMSCs的典型特征。BMSCs移植（ALI+BMSCs）明显减轻了LPS诱导的小鼠ALI。与对照组相比，BMSCs移植显著降低了LPS诱导的ALI小鼠的MPO活性（p<0.05）。与对照组相比，BMSCs移植显著增加了Treg细胞百分比，降低了树突状细胞（DCs）和Th17细胞百分比（p<0.05）。与ALI组相比，BMSCs移植显著提高了LPS诱导的ALI（ALI+BMSCs）中的RvE1和ProD1水平（p<0.05）。与ALI组相比，BMSCs移植显著降低了LPS处理的小鼠（ALI+BMSCs）血清中的IL-6和IL-17水平（p<0.05）。总之，BMSCs移植有效减轻了LPS诱导的小鼠ALI的病理损伤，至少部分是通过促进促消退介质RvE1和ProD1以及调节Treg/Th17平衡实现的。
Zotero 插件