骨髓间充质干细胞通过促进RvE1/ProD1和调节Treg/Th17平衡减轻lps诱导的小鼠急性肺损伤。

He-Bu Qian, Guijuan Zou, Chao Li, Qi-Fang He, Jun Liu
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引用次数: 0

摘要

急性肺损伤(Acute lung injury, ALI)及其重症急性呼吸窘迫综合征(Acute respiratory distress syndrome, ARDS)是由肺泡过度炎症引起的呼吸衰竭,病死率高。本研究探讨骨髓间充质干细胞(BMSCs)对脂多糖(LPS)诱导的ALI肺损伤的影响,并探讨其相关机制。分离培养骨髓间充质干细胞,用CD34和CD44表面标记物染色鉴定。采用LPS诱导ALI小鼠模型,分为ALI组和ALI+BMSCs组。无任何试剂处理的小鼠为对照组,移植骨髓间充质干细胞的小鼠为骨髓间充质干细胞组。流式细胞术检测调节性T (Treg)和Th17百分比。ELISA法检测肺组织中促分解介质(分解素E1 (RvE1)、保护素D1 (ProD1))和血清中细胞因子(白细胞介素6 (IL-6)、IL-17)。测定髓过氧化物酶(MPO)活性。培养的细胞表现出骨髓间充质干细胞的典型特征。骨髓间充质干细胞移植(ALI+BMSCs)可明显减轻lps诱导的小鼠ALI。与对照组相比,骨髓间充质干细胞移植显著降低lps诱导ALI小鼠的MPO活性(p < 0.05)。与对照组相比,骨髓间充质干细胞移植显著提高Treg百分比,降低树突状细胞(dc)和Th17细胞百分比(p < 0.05)。与ALI组相比,骨髓间充质干细胞移植显著提高了lps诱导的ALI (ALI+骨髓间充质干细胞)中RvE1和ProD1水平(p < 0.05)。与ALI组相比,骨髓间充质干细胞移植能显著降低LPS组(ALI+骨髓间充质干细胞)小鼠血清中IL-6和IL-17水平(p < 0.05)。综上所述,骨髓间充质干细胞移植可有效减轻lps诱导的小鼠ALI病理损伤,至少部分是通过促进RvE1和ProD1的分泌以及调节Treg/Th17的平衡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Bone marrow mesenchymal stem cells attenuate LPS-induced acute lung injury in mice by promoting RvE1/ProD1 and modulating Treg/Th17 balance.

Bone marrow mesenchymal stem cells attenuate LPS-induced acute lung injury in mice by promoting RvE1/ProD1 and modulating Treg/Th17 balance.

Bone marrow mesenchymal stem cells attenuate LPS-induced acute lung injury in mice by promoting RvE1/ProD1 and modulating Treg/Th17 balance.

Bone marrow mesenchymal stem cells attenuate LPS-induced acute lung injury in mice by promoting RvE1/ProD1 and modulating Treg/Th17 balance.

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.

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