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间充质干细胞对烟曲霉孢子刺激的巨噬细胞免疫反应的免疫调节作用。

Immunomodulatory effect of mesenchymal stem cells on the immune response of macrophages stimulated by Aspergillus fumigatus conidia.

机构信息

Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea Vaccine Bio Research Institute, The Catholic University of Korea, Seoul, Korea.

Vaccine Bio Research Institute, The Catholic University of Korea, Seoul, Korea.

出版信息

Med Mycol. 2016 May;54(4):377-83. doi: 10.1093/mmy/myv110. Epub 2016 Jan 14.

DOI:10.1093/mmy/myv110
PMID:26768375
Abstract

Mesenchymal stem cells (MSCs) are known to exert potent immunosuppression and anti-inflammatory effects. There is growing interest in their use for immunotherapy for controlling inflammation as well as acute organ injury. However, there are few reports regarding MSC's immunomodulatory effects in the settings of fungal infection. In this study, we attempted to examine the immunomodulatory effects of MSCs in response to Aspergillus fumigatus We measured the cytokine response of murine MSCs on the immune response of murine macrophages (J774A.1 cells) evoked by A. fumigatus conidia. In addition, we evaluated the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the MSC-related cytokine response and fungal growth. As a results, after conidia stimulation, tumor necrosis factor (TNF)-α was down-regulated and interleukin (IL)-10 was up-regulated in MSC-treated J774A.1 cells when compared to J774A.1 cells alone. In addition, fungal growth was reduced in MSC-treated J774A.1 cells when compared to J774A.1 cells, which recovered by GM-CSF. However, the effect of MSCs on the cytokine response was not reversed by GM-CSF. NF-κB translocation decreased in MSC-treated J774A.1 cells compared to J774A.1 cells alone. In conclusion, MSCs demonstrate immunomodulatory properties in both aspects of cytokines and fungal growth. The anti-inflammatory effect of MSCs with regard to cytokine response might be associated with decreased NF-κB translocation, and is not reversed by GM-CSF.

摘要

间充质干细胞(MSCs)具有强大的免疫抑制和抗炎作用。人们对其在免疫治疗中的应用越来越感兴趣,以控制炎症和急性器官损伤。然而,关于 MSCs 在真菌感染中的免疫调节作用的报道很少。在这项研究中,我们试图研究 MSCs 对烟曲霉的免疫调节作用,检测烟曲霉分生孢子对小鼠巨噬细胞(J774A.1 细胞)免疫反应的影响。此外,我们评估了粒细胞-巨噬细胞集落刺激因子(GM-CSF)对 MSC 相关细胞因子反应和真菌生长的影响。结果表明,与单独的 J774A.1 细胞相比,MSC 处理的 J774A.1 细胞中肿瘤坏死因子(TNF)-α下调,白细胞介素(IL)-10 上调。此外,与单独的 J774A.1 细胞相比,MSC 处理的 J774A.1 细胞中的真菌生长减少,而 GM-CSF 则恢复了 J774A.1 细胞中的真菌生长。然而,GM-CSF 并不能逆转 MSC 对细胞因子反应的影响。与单独的 J774A.1 细胞相比,MSC 处理的 J774A.1 细胞中 NF-κB 易位减少。总之,MSC 在细胞因子和真菌生长两方面均表现出免疫调节特性。MSC 对细胞因子反应的抗炎作用可能与 NF-κB 易位减少有关,并且不受 GM-CSF 逆转。

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