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

IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES
Yuxin Yang, XianWang Hu, Shuangshuang Wang, Yongxiang Tian, Keli Yang, Chang Li, Qiong Wu, Wei Liu, Ting Gao, Fangyan Yuan, Rui Guo, Zewen Liu, Yuying Yang, Danna Zhou
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Abstract

Background: Japanese 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.

Results: This 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-1β, CCL-2, and TNF-α), membrane receptors (including RIG-I, TLR3, TLR4, TLR7, and TLR8), NF-κB 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-1α, TNF-α, 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.

Conclusion: Our 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.

迷迭香酸介导的小胶质细胞rig - 1和p62的下调赋予对乙型脑炎病毒诱导的炎症的抗性。
背景:日本脑炎病毒(JEV)是一种蚊媒人畜共患病原体,可引起人类脑炎和猪生殖衰竭。人与动物之间的乙脑病毒传播对公共卫生构成重大威胁,并造成重大经济损失。乙脑感染患者的中枢神经系统过度炎症是导致死亡和残疾的主要原因。迷迭香酸(rorosemary acid, RA)是一种从中草药中分离出来的多羟基酚类化合物,具有抗炎作用,可显著抑制乙脑病毒引起的小鼠神经炎症。结果:本研究探讨了jev感染细胞中RA的抗病毒能力及其潜在机制。结果表明,RA能抑制乙脑病毒的体外复制。采用qPCR、ELISA和Western blot分别检测炎症因子(包括IL-6、IL-1β、CCL-2和TNF-α)、膜受体(包括rig -1、TLR3、TLR4、TLR7和TLR8)、NF-κB复合物和p62/SQSTM1的表达水平。结果表明,RA能显著抑制乙脑感染的BV-2细胞中IL-6、IL-1α、TNF-α和CCL-2的表达,且呈剂量依赖性。此外,RA治疗下调了RIG-I和p62的表达水平,而p62沉默抑制了jev感染的BV-2细胞中炎症细胞因子的上调。结论:我们目前的研究强调了ra介导的rig - 1和p62在小胶质细胞中减少的重要作用,赋予对乙型脑炎病毒诱导的炎症的抵抗力。
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来源期刊
BMC Veterinary Research
BMC Veterinary Research VETERINARY SCIENCES-
CiteScore
4.80
自引率
3.80%
发文量
420
审稿时长
3-6 weeks
期刊介绍: BMC Veterinary Research is an open access, peer-reviewed journal that considers articles on all aspects of veterinary science and medicine, including the epidemiology, diagnosis, prevention and treatment of medical conditions of domestic, companion, farm and wild animals, as well as the biomedical processes that underlie their health.
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