异鼠李素通过RIG-I/JNK途径抑制甲型H1N1流感病毒由干扰素介导的炎症放大。
Isorhamnetin inhibits amplification of influenza A H1N1 virus inflammation mediated by interferon via the RIG-I/JNK pathway.
作者信息
Li Jing, Xu Yifan, Lin Zhiwei, Guan Lili, Chen Shuqi, Zhou Luqian
机构信息
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Institute of Combination Chinese and Western Medicine, Guangzhou Medical University, Guangzhou, China.
出版信息
Ann Transl Med. 2021 Aug;9(16):1327. doi: 10.21037/atm-21-3532.
BACKGROUND
Interferon (IFN) amplifies the influenza virus-mediated inflammatory response by forming a paracrine signal feedback loop, which is considered an important cause of excessive inflammatory damage. Isorhamnetin has a wide spectrum of beneficial pharmacological properties, including anti-inflammatory and antiviral effects. The regulatory effect and mechanism of isorhamnetin on influenza virus-mediated inflammation have not yet been reported.
METHODS
We pre-treated A549 cells with IFN-β (50 ng/mL) for 4 h followed by IAV (H1N1) infection to simulate the inflammation amplification effect caused by the paracrine effect of IFN-β. The anti-inflammation activity of isorhamnetin against amplification inflammation of interferon mediated by IAV (H1N1) was assessed by performing quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay (ELISA) in A549 cells.
RESULTS
Compared with the virus infection group, the IFN-β pretreatment virus infection group had an upregulated level of pro-inflammatory cytokine expression, which was inhibited by isorhamnetin significantly via the retinoic acid-induced gene I (RIG-I)/c-Jun N-terminal kinase (JNK) signaling pathway. Molecular docking studies further verified that isorhamnetin can interact with JNK.
CONCLUSIONS
Our work was the first to demonstrate the anti-inflammatory activity and mechanism of isorhamnetin during influenza virus infection. Isorhamnetin significantly improves the excessive inflammatory response mediated by IAV (H1N1) infection mainly via the RIG-I/JNK pathway. Additionally, isorhamnetin exhibited an apparent antiviral effect of H1N1 .
背景
干扰素（IFN）通过形成旁分泌信号反馈回路来放大流感病毒介导的炎症反应，这被认为是过度炎症损伤的重要原因。异鼠李素具有广泛的有益药理特性，包括抗炎和抗病毒作用。异鼠李素对流感病毒介导的炎症的调节作用及机制尚未见报道。
方法
我们先用IFN-β（50 ng/mL）预处理A549细胞4小时，然后进行甲型流感病毒（H1N1）感染，以模拟IFN-β旁分泌效应引起的炎症放大效应。通过在A549细胞中进行定量实时聚合酶链反应（qRT-PCR）、蛋白质印迹法和酶联免疫吸附测定（ELISA），评估异鼠李素对甲型流感病毒（H1N1）介导的干扰素放大炎症的抗炎活性。
结果
与病毒感染组相比，IFN-β预处理病毒感染组促炎细胞因子表达水平上调，而异鼠李素通过维甲酸诱导基因I（RIG-I）/c-Jun氨基末端激酶（JNK）信号通路显著抑制了该上调。分子对接研究进一步证实异鼠李素可与JNK相互作用。
结论
我们的研究首次证明了异鼠李素在流感病毒感染期间的抗炎活性及机制。异鼠李素主要通过RIG-I/JNK途径显著改善甲型流感病毒（H1N1）感染介导的过度炎症反应。此外，异鼠李素对H1N1表现出明显的抗病毒作用。
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