Rosmarinic acid-mediated downregulation of RIG-I and p62 in microglia confers resistance to Japanese encephalitis virus-induced inflammation

文献类型： 外文期刊

第一作者： Yang, Yuxin

作者： Yang, Yuxin;Yang, Yuying;Hu, Xianwang;Wang, Shuangshuang;Tian, Yongxiang;Yang, Keli;Li, Chang;Wu, Qiong;Liu, Wei;Gao, Ting;Yuan, Fangyan;Guo, Rui;Liu, Zewen;Zhou, Danna;Hu, Xianwang;Wang, Shuangshuang;Tian, Yongxiang;Yang, Keli;Li, Chang;Wu, Qiong;Liu, Wei;Gao, Ting;Yuan, Fangyan;Guo, Rui;Liu, Zewen;Zhou, Danna

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关键词： Japanese encephalitis virus; Anti-inflammatory; Rosmarinic acid; RIG-I; p62

期刊名称：BMC VETERINARY RESEARCH （ 影响因子：2.6； 五年影响因子：2.7 ）

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年卷期： 2024 年 20 卷 1 期

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收录情况： SCI

摘要： BackgroundJapanese encephalitis virus (JEV) is a mosquito-borne zoonotic pathogen that causes encephalitis in humans and reproductive failure in pigs. The transmission of JEV between humans and animals poses a significant public health threat and results in substantial economic losses. Excessive inflammation in the central nervous system of JEV-infected patients is a major cause of mortality and disability. Rosmarinic acid (RA), a polyhydroxyphenolic compound isolated from medicinal herbs, has been preliminarily shown to possess anti-inflammatory properties and significantly inhibit JEV-induced neuroinflammation in mice.ResultsThis study investigated the antiviral capacity and potential mechanisms of RA in JEV-infected cells. The results demonstrated that RA could inhibit JEV replication in vitro. Furthermore, the expression levels of inflammatory cytokines (including IL-6, IL-1 beta, CCL-2, and TNF-alpha), membrane receptors (including RIG-I, TLR3, TLR4, TLR7, and TLR8), NF-kappa B complex and p62/SQSTM1 were assessed using qPCR, ELISA, and Western blot, respectively. The findings indicated that RA significantly suppressed the expression of IL-6, IL-1 alpha, TNF-alpha, and CCL-2 in JEV-infected BV-2 cells in a dose-dependent manner. Additionally, RA treatment downregulated the expression levels of RIG-I and p62, while p62 silencing inhibited the upregulation of inflammatory cytokines in JEV-infected BV-2 cells.ConclusionOur present study highlights the important role of RA-mediated reduction of RIG-I and p62 in microglia, conferring resistance to Japanese encephalitis virus-induced inflammation.

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