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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.
International Journal of Immunopathology and Pharmacology ( IF 3.0 ) Pub Date : 2019-04-18 , DOI: 10.1177/2058738419844932
Mamdooh H Ghoneum 1 , James K Gimzewski 2, 3 , Aya D Ghoneum 2 , Sudhanshu Agrawal 4
Affiliation  

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.

中文翻译:

MRN-100(一种铁基化合物)在上调人树突状细胞中细胞因子IL-10的产生以促进体外抗炎反应中的潜在作用。

研究了高铁酸氢盐流体MRN-100(一种具有强抗氧化剂特性的铁基化合物),以确定其在体外对人树突状细胞(DC)的可能的抗炎作用。将人类单核细胞衍生的DC用两种浓度(50和100μL/ mL)的MRN-100处理24小时,然后用或不用脂多糖(LPS)刺激。通过流式细胞术评估DC成熟标志物的表达,并通过酶联免疫吸附测定(ELISA)确定细胞因子的产生。通过将MRN-100处理过的和未处理过的DC与同种幼稚的CD4 + T细胞共培养,并分析T细胞的细胞因子生成来进行功能分析。结果显示,用MRN-100进行的治疗虽然不显着,但显着上调了共刺激分子CD80和CD86,并增加了人类白细胞抗原-DR(HLA-DR)。MRN-100处理还显着增加了抗炎细胞因子白介素(IL)-10的产生。另一方面,MRN-100仅在高浓度时才显着诱导促炎性细胞因子如IL-6的分泌。此外,用MRN-100预处理且未用LPS刺激的DC能够引发CD4 + T细胞分泌大量IL-10,同时抑制促炎性细胞因子肿瘤坏死因子(TNF)-α的分泌。这些结果表明,MRN-100是强有力的抗炎剂,其在体外促进抗炎免疫反应的产生。
更新日期:2019-11-01
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