5-Hydroxymethylfurfural Enhances the Antiviral Immune Response in Macrophages through the Modulation of RIG-I-Mediated Interferon Production and the JAK/STAT Signaling Pathway.
5-Hydroxymethylfurfural Enhances the Antiviral Immune Response in Macrophages through the Modulation of RIG-I-Mediated Interferon Production and the JAK/STAT Signaling Pathway.
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5-羟甲基糠醛通过调节 RIG-I 介导的干扰素产生和 JAK/STAT 信号通路增强巨噬细胞的抗病毒免疫反应
DOI：
10.1021/acsomega.1c03862
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发表时间：
2021-10-26
期刊：
影响因子：
4.1
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Zou H;Wu T;Wang Y;Kang Y;Shan Q;Xu L;Jiang Z;Lin X;Ye XY;Xie T;Zhang H
5-羟甲基呋喃(5-HMF)广泛存在于糖类食品和中药材中。5-HMF在抗病毒先天免疫中的作用及其机制尚未见报道。在这项研究中，我们首次揭示了5-HMF上调维甲酸诱导基因I(RIG-I)介导的I型干扰素(干扰素)的产生作为对病毒感染的反应。水泡性口炎病毒诱导的干扰素-β和干扰素刺激的趋化因子基因在RAW264.7细胞和原代培养的腹膜巨噬细胞中表达上调，5-羟甲基呋喃是一种天然产物，似乎抑制病毒复制的效率。同时，5-羟甲基纤维素预处理的小鼠表现出增强的先天抗病毒免疫，增加了血清干扰素-β的水平，并降低了感染病毒后的发病率和病毒载量。由此可见，5-HMF对促进I型干扰素的产生有积极作用。从机制上讲，5-HMF上调巨噬细胞RIG-I的表达，加速RIG-I信号通路的激活。此外，在5-α/β联合处理的巨噬细胞中，STAT1和STAT2的磷酸化以及干扰素刺激的趋化因子基因的表达也被增强。综上所述，这些发现表明，5-HMF不仅可以诱导I型干扰素的产生，还可以增强干扰素-JAK/STAT信号转导，从而产生一种新的抗病毒感染的免疫调节机制。总之，我们的研究揭示了5-HMF在抗病毒天然免疫反应中以前未被认识到的作用，并提示了利用5-HMF控制病毒感染的新潜力。
5-Hydroxymethylfurfural (5-HMF) exists in a wide range of sugar-rich foods and traditional Chinese medicines. The role of 5-HMF in antiviral innate immunity and its mechanism have not been reported previously. In this study, we reveal for the first time that 5-HMF upregulates the production of retinoic acid-inducible gene I (RIG-I)-mediated type I interferon (IFN) as a response to viral infection. IFN-β and IFN-stimulated chemokine gene expressions induced by the vesicular stomatitis virus (VSV) are upregulated in RAW264.7 cells and primary peritoneal macrophages after treatment with 5-HMF, a natural product that appears to inhibit the efficiency of viral replication. Meanwhile, 5-HMF-pretreated mice show enhanced innate antiviral immunity, increased serum levels of IFN-β, and reduced morbidity and viral loads upon infection with VSV. Thus, 5-HMF can be seen to have a positive effect on enhancing type I IFN production. Mechanistically, 5-HMF upregulates the expression of RIG-I in macrophages, resulting in an acceleration of the RIG-I signaling pathway activation. Additionally, STAT1 and STAT2 phosphorylations, along with the expression of IFN-stimulated chemokine genes induced by IFN-α/β, were also enhanced in macrophages cotreated with 5-HMF. In summary, these findings indicate that 5-HMF not only can induce type I IFN production but also can enhance IFN-JAK/STAT signaling, leading to a novel immunomodulatory mechanism against viral infection. In conclusion, our study reveals a previously unrecognized effect of 5-HMF in the antiviral innate immune response and suggests new potential of utilizing 5-HMF for controlling viral infection.
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影响因子：
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作者：
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