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钙三醇处理的间充质干细胞作为免疫调节微环境对小鼠变应性哮喘的影响。

Effect of Calcitriol Treated Mesenchymal Stem Cells as an Immunomodulation Micro-environment on Allergic Asthma in a Mouse Model.

机构信息

Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Applied Virology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

出版信息

Endocr Metab Immune Disord Drug Targets. 2023;23(8):1096-1103. doi: 10.2174/1871530323666230127115847.

Abstract

BACKGROUND

Allergic asthma is a chronic inflammatory illness of the respiratory system characterized by an increase in the number of inflammatory cells in the airways and trouble breathing. Mesenchymal stem cells (MSCs) have the potential to be used in inflammatory diseases as a cellular immunosuppressive treatment. They express calcitriol receptors and communicate with other immunocytes, which increases their anti-inflammatory activity. This study aimed to determine the effects of calcitriol-treated MSC treatment on allergic asthma pathways in a mouse model.

METHODS

To generate a mouse model of asthma, the mice were sensitized intraperitoneally with ovalbumin (OVA) and aluminum hydroxide emulsion and then challenged intra-nasally with OVA. On day 14, experimental mice received tail vein injections of calcitriol-treated MSCs in PBS prior to allergen exposure. The cytokines assays including IL-4, 10, 12, 17, TGF-β and IFN-γ, splenocytes proliferation, and histological examination of lungs samples were performed. The mice were sensitized with OVA and the response to dexamethasone treatment was compared.

RESULTS

Calcitriol-treated MSCs significantly increased the levels of IL-12, TGF-β, and IFN-γ compared to non-treated MSCs groups. Moreover, calcitriol-treated and non-treated MSCs significantly decreased IL-4 and IL-17 compared to asthmatic groups. The results of the histopathological examination showed that calcitriol-treated MSCs reduced the accumulation of inflammatory cells and bronchial wall thickening in comparison with the asthma group.

CONCLUSION

Using the allergic asthma model, we were able to show that calcitriol-treated MSCs had an inhibitory impact on airway inflammation. Our findings suggest that the injection of calcitrioltreated MSCs may be a viable treatment option for allergic asthma.

摘要

背景

过敏性哮喘是一种呼吸系统的慢性炎症性疾病,其特征是气道中炎症细胞数量增加和呼吸困难。间充质干细胞(MSCs)具有作为细胞免疫抑制治疗在炎症性疾病中应用的潜力。它们表达钙三醇受体并与其他免疫细胞相互交流,从而增强其抗炎活性。本研究旨在确定钙三醇处理的 MSC 治疗对哮喘小鼠模型中哮喘途径的影响。

方法

为了建立哮喘小鼠模型,将小鼠用卵清蛋白(OVA)和氢氧化铝乳液腹膜内致敏,然后用 OVA 鼻内攻击。在第 14 天,实验小鼠在过敏原暴露前通过尾静脉注射 PBS 中的钙三醇处理的 MSC。进行细胞因子检测,包括 IL-4、10、12、17、TGF-β 和 IFN-γ、脾细胞增殖和肺组织样本的组织学检查。将小鼠用 OVA 致敏,并比较对地塞米松治疗的反应。

结果

与未处理的 MSC 组相比,钙三醇处理的 MSC 显著增加了 IL-12、TGF-β 和 IFN-γ 的水平。此外,钙三醇处理和未处理的 MSC 与哮喘组相比,显著降低了 IL-4 和 IL-17 的水平。组织病理学检查结果表明,与哮喘组相比,钙三醇处理的 MSC 减少了炎症细胞的积聚和支气管壁增厚。

结论

使用过敏性哮喘模型,我们能够表明钙三醇处理的 MSC 对气道炎症具有抑制作用。我们的研究结果表明,注射钙三醇处理的 MSC 可能是治疗过敏性哮喘的一种可行选择。

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