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深入了解镁在间充质干细胞免疫调节特性中的作用。

An insight into the role of magnesium in the immunomodulatory properties of mesenchymal stem cells.

机构信息

Department of Food and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.

Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.

出版信息

J Nutr Biochem. 2018 May;55:200-208. doi: 10.1016/j.jnutbio.2018.02.006. Epub 2018 Feb 13.

DOI:10.1016/j.jnutbio.2018.02.006
PMID:29554498
Abstract

Magnesium (Mg) is a mineral with the ability to influence cell proliferation and to modulate inflammatory/immune responses, due to its anti-inflammatory properties. In addition, mesenchymal stem cells (MSCs) modulate the function of all major immune cell populations. Knowing that, the current work aimed to investigate the effects of Mg enrichment, and its influence on the immunomodulatory capacity of MSCs. Murine C3H/10T1/2 MSCs were cultivated in media with different concentrations of Mg (0, 1, 3 and 5 mM), in order to evaluate the effects of Mg on MSC immunomodulatory properties, cell proliferation rates, expression of NFκB and STAT-3, production of IL-1β, IL-6, TGF-β, IL-10, PGE2 and NO, and TRPM7 expression. The results showed that TRPM7 is expressed in MSCs, but Mg, in the way that cells were cultivated, did not affect TRPM7 expression. Additionally, there was no difference in the intracellular concentration of Mg. Mg, especially at 5 mM, raised proliferation rates of MSCs, and modulated immune responses by decreasing levels of IL-1β and IL-6, and by increasing levels of IL-10 and PGE2 in cells stimulated with LPS or TNF-α. In addition, MSCs cultured in 5 mM Mg expressed lower levels of pNFκB/NFκB and higher levels of pSTAT-3/STAT-3. Furthermore, conditioned media from MSCs reduced lymphocyte and macrophage proliferation, but Mg did not affect this parameter. In addition, conditioned media from MSCs cultured at 5 mM of Mg modulated the production profile of cytokines, especially of IL-1β and IL-6 in macrophages. In conclusion, Mg is able to modulate some immunoregulatory properties of MSCs.

摘要

镁(Mg)是一种具有调节炎症/免疫反应能力的矿物质,这是由于其抗炎特性。此外,间充质干细胞(MSCs)调节所有主要免疫细胞群的功能。鉴于此,目前的工作旨在研究镁富集及其对 MSCs 免疫调节能力的影响。用不同浓度的 Mg(0、1、3 和 5 mM)培养小鼠 C3H/10T1/2 MSCs,以评估 Mg 对 MSC 免疫调节特性、细胞增殖率、NFκB 和 STAT-3 表达、IL-1β、IL-6、TGF-β、IL-10、PGE2 和 NO 产生以及 TRPM7 表达的影响。结果表明,TRPM7 在 MSCs 中表达,但细胞培养方式的 Mg 并没有影响 TRPM7 的表达。此外,细胞内 Mg 浓度没有差异。Mg(尤其是 5 mM)提高了 MSCs 的增殖率,并通过降低 LPS 或 TNF-α刺激的细胞中 IL-1β 和 IL-6 的水平,以及增加 IL-10 和 PGE2 的水平来调节免疫反应。此外,在 5 mM Mg 中培养的 MSCs 表达较低水平的 pNFκB/NFκB 和较高水平的 pSTAT-3/STAT-3。此外,MSCs 的条件培养基可减少淋巴细胞和巨噬细胞的增殖,但 Mg 不影响这一参数。此外,在 5 mM Mg 中培养的 MSCs 的条件培养基调节细胞因子的产生谱,尤其是巨噬细胞中 IL-1β 和 IL-6 的产生谱。总之,Mg 能够调节 MSCs 的一些免疫调节特性。

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