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MRN-100(一种基于铁的化合物)在体外通过上调人树突状细胞细胞因子 IL-10 的产生来发挥抗炎作用的潜在作用。

Potential role of MRN-100, an iron-based compound, in upregulating production of cytokine IL-10 in human dendritic cells to promote an anti-inflammatory response in vitro.

机构信息

1 Department of Surgery, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA.

2 Department of Chemistry & Biochemistry, UCLA, Los Angeles, CA, USA.

出版信息

Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738419844932. doi: 10.1177/2058738419844932.

Abstract

The hydroferrate fluid MRN-100, an iron-based compound with potent antioxidant characteristics, was examined to identify its possible anti-inflammatory effects on human dendritic cells (DCs) in vitro. Human monocyte-derived DCs were treated with MRN-100 at two concentrations (50 and 100 μL/mL) for 24 h and then stimulated with or without lipopolysaccharides (LPS). The expression of DC maturation markers was assessed by flow cytometry and the production of cytokines was determined by enzyme-linked immunosorbent assay (ELISA). Functional assay was performed by co-culturing MRN-100-treated and untreated DCs with allogeneic naïve CD4+ T cells and assaying the T cells' cytokine production. Results show that treatment with MRN-100 significantly upregulated the co-stimulatory molecules CD80 and CD86 and increased human leukocyte antigen-DR (HLA-DR) though not significantly. MRN-100 treatment also significantly increased the production of the anti-inflammatory cytokine interleukin (IL)-10. On the other hand, MRN-100 significantly induced the secretion of pro-inflammatory cytokines such as IL-6 only at high concentrations. Furthermore, DCs pretreated with MRN-100 and either stimulated or not with LPS were able to prime CD4+ T cells to secrete significant amounts of IL-10 while inhibiting the secretion of pro-inflammatory cytokine tumor necrosis factor (TNF)-α. These results indicate that MRN-100 is a powerful anti-inflammatory agent that promotes the generation of an anti-inflammatory immune response in vitro. MRN-100 could be beneficial for treating patients with inflammatory diseases, including arthritis and type 1 diabetes, and its potential benefits should be examined in clinical trials.

摘要

水合铁酸盐流体 MRN-100 是一种具有强大抗氧化特性的铁基化合物,本研究旨在探讨其在体外对人树突状细胞(DC)的抗炎作用。将人单核细胞来源的 DC 分别用 MRN-100(浓度分别为 50 和 100 μL/mL)处理 24 h 后,用或不用脂多糖(LPS)进行刺激。通过流式细胞术检测 DC 成熟标志物的表达,通过酶联免疫吸附试验(ELISA)检测细胞因子的产生。通过共培养经 MRN-100 处理和未经处理的 DC 与同种异体幼稚 CD4+T 细胞,并检测 T 细胞细胞因子的产生,进行功能测定。结果显示,MRN-100 处理可显著上调共刺激分子 CD80 和 CD86 的表达,并增加人类白细胞抗原-DR(HLA-DR)的表达(尽管无统计学意义)。MRN-100 处理还可显著增加抗炎细胞因子白细胞介素(IL)-10 的产生。另一方面,MRN-100 仅在高浓度时可显著诱导促炎细胞因子如 IL-6 的分泌。此外,用 MRN-100 预处理后再用 LPS 刺激或不刺激的 DC 能够刺激 CD4+T 细胞分泌大量的 IL-10,同时抑制促炎细胞因子肿瘤坏死因子(TNF)-α的分泌。这些结果表明,MRN-100 是一种强大的抗炎剂,可在体外促进抗炎免疫反应的产生。MRN-100 可能有益于治疗炎症性疾病患者,包括关节炎和 1 型糖尿病,其潜在益处应在临床试验中进行评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57bf/6472165/3b681ce9e0da/10.1177_2058738419844932-fig1.jpg

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