Background

Mesenchymal stromal/stem cells (MSCs) are multi-potent non-hematopoietic stem cells, residing in most tissues including the lung. MSCs have been used in therapy of chronic inflammatory lung diseases such as Cystic Fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD) but the main beneficial effects reside in the anti-inflammatory potential of the released extracellular vesicles (EVs). Recent reports demonstrate that EVs are effective in animal model of asthma, E.coli pneumonia, lung ischemia-reperfusion, and virus airway infection among others. Despite this growing literature, the EVs effects on CF are largely unexplored.

Methods

We treated IB3-1 cells, an in vitro human model of CF, with EVs derived from human lung MSCs under basal and inflammatory conditions (TNFα stimulation).

Results

We demonstrated here that treatment of IB3-1 CF cell line with EVs, down-regulates transcription and protein expression of pro-inflammatory cytokines such as IL-1β, IL-8, IL-6 under TNFα - stimulated conditions. EVs treatment upregulates the mRNA expression of PPARγ, a transcription factor controlling anti-inflammatory and antioxidant mechanisms via NF-kB and HO-1. Accordingly, NF-kB nuclear translocation is reduced resulting in impairment of the downstream inflammation cascade. In addition, the mRNA of HO-1 is enhanced together with the antioxidant defensive response of the cells.

Conclusions

We conclude that the anti-inflammatory and anti-oxidant efficacy of EVs derived from lung MSCs could be mediated by up-regulation of the PPARγ axis, whose down-stream effectors (NF-kB and HO-1) are well-known modulators of these pathways.

General significance

EVs could be a novel strategy to control the hyper-inflamed condition in Cystic Fibrosis.

中文翻译：

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肺间充质干细胞来源的细胞外囊泡减轻囊性纤维化上皮细胞的炎症反应

背景

间充质基质/干细胞（MSC）是多潜能的非造血干细胞，存在于包括肺在内的大多数组织中。MSC已用于治疗慢性炎症性肺疾病，如囊性纤维化（CF），哮喘和慢性阻塞性肺疾病（COPD），但主要的有益作用在于释放的细胞外囊泡（EVs）的抗炎潜力。最近的报道表明，电动汽车在哮喘，大肠杆菌肺炎，肺缺血-再灌注和病毒气道感染等动物模型中均有效。尽管有越来越多的文献报道，但电动汽车对CF的影响仍未得到充分开发。

方法

我们在基础和炎症条件下（TNFα刺激），用衍生自人肺MSC的EVs处理IB3-1细胞（一种体外CF人体模型）。

结果

我们在此证明，用EV处理IB3-1 CF细胞系可在TNFα刺激的条件下下调促炎性细胞因子（如IL-1β，IL-8，IL-6）的转录和蛋白质表达。电动汽车的治疗可上调PPARγ的mRNA表达，PPARγ是通过NF-kB和HO-1控制抗炎和抗氧化机制的转录因子。因此，NF-kB核易位减少，导致下游炎症级联的损伤。另外，HO-1的mRNA与细胞的抗氧化防御反应一起增强。

结论

我们得出的结论是，肺间充质干细胞衍生的电动汽车的抗炎和抗氧化功效可能是由PPARγ轴的上调介导的，PPARγ轴的下游效应器（NF-kB和HO-1）是PPARγ轴的众所周知的调节剂。这些途径。

一般意义

电动汽车可能是控制囊性纤维化过度发炎的一种新策略。