Mangiferin inhibits macrophage classical activation via downregulating interferon regulatory factor 5 expression.
Mangiferin inhibits macrophage classical activation via downregulating interferon regulatory factor 5 expression.
复制标题
芒果苷通过下调干扰素调节因子 5 表达抑制巨噬细胞经典激活
DOI：
10.3892/mmr.2016.5352
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发表时间：
2016-08
影响因子：
3.4
通讯作者：
Deng J
中科院分区：
文献类型：
--
作者：
Wei Z;Yan L;Chen Y;Bao C;Deng J;Deng J
芒果苷是一种天然多酚，是芒果叶的主要有效成分。数百年来，芒果叶一直作为多种中药制剂的成分用于治疗支气管炎。然而，芒果苷治疗支气管炎的药理机制仍有待阐明。巨噬细胞经典激活在支气管气道炎症过程中起重要作用，干扰素调节因子5（IRF5）已被确定为巨噬细胞经典激活的关键调节因子。本研究利用人单核细胞系THP - 1，在体外研究芒果苷是否通过抑制IRF5表达来抑制巨噬细胞经典激活。THP - 1细胞经佛波酯12 - 肉豆蔻酸13 - 乙酸酯诱导分化为巨噬细胞。巨噬细胞经脂多糖（LPS）/干扰素 - γ（IFN - γ）刺激后极化为M1巨噬细胞。采用流式细胞术分析检测M1巨噬细胞。逆转录 - 定量聚合酶链反应用于研究细胞IRF5基因表达。细胞培养和细胞匀浆后，采用酶联免疫吸附测定法评估促炎细胞因子和IRF5的水平。利用激光扫描共聚焦显微镜免疫荧光分析对巨噬细胞中IRF5蛋白和细胞核进行共定位。本研究结果表明，芒果苷在体外显著抑制LPS/IFN - γ刺激诱导的巨噬细胞经典激活，并显著减少促炎细胞因子的释放。此外，细胞IRF5表达显著下调。这些结果提示，芒果苷对巨噬细胞经典激活的抑制作用可能是通过下调细胞IRF5表达水平来实现的。
Mangiferin is a natural polyphenol and the predominant effective component of Mangifera indica Linn. leaves. For hundreds of years, Mangifera indica Linn. leaf has been used as an ingredient in numerous traditional Chinese medicine preparations for the treatment of bronchitis. However, the pharmacological mechanism of mangiferin in the treatment of bronchitis remains to be elucidated. Macrophage classical activation is important role in the process of bronchial airway inflammation, and interferon regulatory factor 5 (IRF5) has been identified as a key regulatory factor for macrophage classical activation. The present study used the THP-1 human monocyte cell line to investigate whether mangiferin inhibits macrophage classical activation via suppressing IRF5 expression in vitro. THP-1 cells were differentiated to macrophages by phorbol 12-myristate 13-acetate. Macrophages were polarized to M1 macrophages following stimulation with lipopolysaccharide (LPS)/interferon-γ (IFN-γ). Flow cytometric analysis was conducted to detect the M1 macrophages. Reverse transcription-quantitative polymerase chain reaction was used to investigate cellular IRF5 gene expression. Levels of proinflammatory cytokines and IRF5 were assessed following cell culture and cellular homogenization using enzyme-linked immunosorbent assay. IRF5 protein and nuclei co-localization was performed in macrophages with laser scanning confocal microscope immunofluorescence analysis. The results of the present study demonstrated that mangiferin significantly inhibits LPS/IFN-γ stimulation-induced classical activation of macrophages in vitro and markedly decreases proinflammatory cytokine release. In addition, cellular IRF5 expression was markedly downregulated. These results suggest that the inhibitory effect of mangiferin on classical activation of macrophages may be exerted via downregulation of cellular IRF5 expression levels.