Naringenin inhibits dendritic cell maturation and has therapeutic effects in a murine model of collagen-induced arthritis
Naringenin inhibits dendritic cell maturation and has therapeutic effects in a murine model of collagen-induced arthritis
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DOI：
10.1016/j.jnutbio.2015.07.016
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发表时间：
2015-12-01
影响因子：
5.6
通讯作者：
Lin, Chi-Chen
中科院分区：
文献类型：
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作者：
Li, Yi-Rong;Chen, Der-Yuan;Lin, Chi-Chen
本研究的目的是研究柚皮素（5，7，4 '-三羟基黄烷酮），柑橘类黄酮，对树突状细胞（DC）成熟的影响，以及其作为胶原诱导的关节炎（CIA）小鼠模型中的治疗剂的潜力。当以非细胞毒性剂量给予时，柚苷素有效地抑制脂多糖（LPS）诱导的DC成熟，表现为促炎细胞因子/趋化因子的产生、共刺激分子的表达和DC的Ag特异性T细胞引发能力的减少。此外，降低LPS诱导的MAPK和NF-κ B信号通路的激活可能有助于柚皮素的抑制活性。在CIA小鼠中，口服柚皮素可改善关节炎的严重程度，降低抗II型胶原（CII）IgG的水平，并限制T细胞的增殖，观察到CII再刺激后脾脏中Th 1和Th 17细胞的频率较低。总之，这项研究首次表明，柚皮素可以操纵DC的免疫刺激特性，因此代表了治疗人类类风湿性关节炎的潜在治疗方法。(C)2015 Elsevier Inc. All rights reserved.
The aim of this study was to investigate the effect of naringenin (5,7,4'-trihydroxyflavanone), a citrus flavonoid, on dendritic cell (DC) maturation, as well as its potential as a therapeutic agent in a murine model of collagen-induced arthritis (CIA). Naringenin effectively inhibited lipopolysaccharide (LPS)-induced DC maturation as shown by reductions in the production of proinflammatory cytokines/chemokines, the expression of costimulatory molecules and the Ag-specific T cell priming ability of DCs when given at noncytotoxic doses. In addition, the decrease of LPS-induced MAPK and NF-kappa B signaling activation may contribute to the inhibitory activity of naringenin. In mice with CIA, the oral administration of naringenin ameliorated the severity of arthritis, reduced the levels of anticollagen Type II (CII) IgG and limited the proliferation of T cells, observed as a lower frequency of Th1 and Th17 cells in the spleen after restimulation with CII. In conclusion, this study shows for the first time that naringenin can manipulate the immunostimulatory properties of DCs and thus represents a potential therapeutic for the treatment of rheumatoid arthritis in humans. (C) 2015 Elsevier Inc. All rights reserved.