Laboratory of Experimental Hematology, Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Lineu Prestes, 580 - Bloco 17., São Paulo, SP, 05508-900, Brazil.
Stem Cell Rev Rep. 2017 Aug;13(4):482-490. doi: 10.1007/s12015-017-9746-0.
Glutamine (GLUT) is a nonessential amino acid that can become conditionally essential under stress conditions, being able to act in the modulation of the immune responses. Mesenchymal stem cells (MSCs) are known to their capability in the modulation of immune responses through cell-cell contact and by the secretion of soluble factors. Considering that GLUT is an immunonutrient and little is known about the influence of GLUT on the capability of MSCs to modulate immune cells, this work aims to investigate how variations in GLUT concentrations in vitro could affect some immunomodulatory properties of MSCs. In order to evaluate the effects of GLUT on MSCs immunomodulatory properties, cell proliferation rates, the expression of NFκB and STAT-3, and the production of IL-1β, IL-6, IL-10, TGF-β and TNF-α by MSCs were assessed. Based on our findings, GLUT at high doses (10 mM) augmented the proliferation of MSCs and modulated immune responses by decreasing levels of pro-inflammatory cytokines, such as IL-1β and IL-6, and by increasing levels of anti-inflammatory cytokines IL-10 and TGF-β. In addition, MSCs cultured in higher GLUT concentrations (10 mM) expressed lower levels of NF-κB and higher levels of STAT-3. Furthermore, conditioned media from MSCs cultured at higher GLUT concentrations (10 mM) reduced lymphocyte and macrophage proliferation, increased IL-10 production by both cells types, and decreased IFN-γ production by lymphocytes. Overall, this study showed that 10 mM of GLUT is able to modify immunomodulatory properties of MSCs.
谷氨酰胺（GLUT）是一种非必需氨基酸，在应激条件下可能成为条件必需氨基酸，能够调节免疫反应。间充质干细胞（MSCs）以其通过细胞-细胞接触和分泌可溶性因子来调节免疫反应的能力而闻名。考虑到 GLUT 是一种免疫营养素，并且对于 GLUT 对 MSCs 调节免疫细胞的能力的影响知之甚少，本研究旨在探讨体外 GLUT 浓度的变化如何影响 MSCs 的一些免疫调节特性。为了评估 GLUT 对 MSCs 免疫调节特性的影响，评估了 MSC 的细胞增殖率、NFκB 和 STAT-3 的表达以及 MSC 产生的 IL-1β、IL-6、IL-10、TGF-β 和 TNF-α。基于我们的发现，高剂量（10 mM）的 GLUT 增强了 MSC 的增殖，并通过降低促炎细胞因子（如 IL-1β 和 IL-6）的水平和增加抗炎细胞因子 IL-10 和 TGF-β 的水平来调节免疫反应。此外，在较高 GLUT 浓度（10 mM）下培养的 MSC 表达较低水平的 NF-κB 和较高水平的 STAT-3。此外，在较高 GLUT 浓度（10 mM）下培养的 MSC 的条件培养基减少了淋巴细胞和巨噬细胞的增殖，增加了两种细胞类型的 IL-10 产生，并减少了淋巴细胞的 IFN-γ 产生。总体而言，这项研究表明，10 mM 的 GLUT 能够改变 MSC 的免疫调节特性。
