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Effect of Emodin on Coxsackievirus B3m-Mediated Encephalitis in Hand, Foot, and Mouth Disease by Inhibiting Toll-Like Receptor 3 Pathway In Vitro and In Vivo.
The Journal of Infectious Diseases ( IF 6.4 ) Pub Date : 2020-03-02 , DOI: 10.1093/infdis/jiaa093
Yan Ding 1 , Jie Xu 2, 3 , Liang-Bin Cheng 4 , Yong-Qian Huang 5 , You-Qin Wang 6 , Hui Li 7 , Yu Li 8 , Jing-Yu Ji 9 , Ji-Hong Zhang 3 , Lei Zhao 10
Affiliation  

BACKGROUND Encephalitis in Hand, Foot and Mouth Disease is a serious threat to children's health and life. Toll-like receptor 3 is an innate immune-recognition receptor which can recognize virus and initiate innate immune responses. Emodin have the effects of anti-inflammatory and regulating immune function, but the mechanism is not very clear. METHODS Cells and mice were pre-treated with CVB3 and treated with emodin. The mRNA and protein levels of TLR3 and downstream molecules were respectively detected by qT-PCR and Western-Blotting. TLR3 expression was also down-regulated by anti-TLR3Ab or siRNA. Pathological changes were assessed with H&E staining. Immunohistochemistry was used to examine the expression of TLR3 in brain tissues.The expression of IL-6, NF-κB and IFN-β in serum were tested with ELISA. RESULTS Emodin decreased the mRNA and protein levels of TLR3 and downstream molecules in vitro and in vivo. After down-regulating TLR3 using anti-TLR3Ab or siRNA, emodin could still decrease the mRNA and protein levels of TLR3 and downstream molecules. Emodin also displayed notable effects on pathology, TLR3 protein in brain tissues and expression of IL-6, NF-κB, IFN-β in serum. CONCLUSIONS Emodin exerts a protective effect in CVB3 mediated-encephalitis in HFMD by inhibiting the TLR3 pathway.

中文翻译:

大黄素通过抑制Toll-like Receptor 3的体内外途径对柯萨奇B3m介导的手足口病脑炎的影响。

背景技术手足口病脑炎是对儿童健康和生命的严重威胁。Toll样受体3是一种先天免疫识别受体,可以识别病毒并启动先天免疫应答。大黄素具有抗炎和调节免疫功能的作用,但机理尚不十分清楚。方法将细胞和小鼠用CVB3预处理,并用大黄素处理。通过qT-PCR和Western-Blotting分别检测TLR3和下游分子的mRNA和蛋白质水平。TLR3表达也被抗TLR3Ab或siRNA下调。用H&E染色评估病理变化。免疫组织化学法检测脑组织中TLR3的表达。ELISA法检测血清中IL-6,NF-κB和IFN-β的表达。结果大黄素在体内外降低了TLR3和下游分子的mRNA和蛋白水平。大黄素在使用抗TLR3Ab或siRNA下调TLR3后,仍可以降低TLR3和下游分子的mRNA和蛋白水平。大黄素对脑组织的病理学,TLR3蛋白和血清中IL-6,NF-κB,IFN-β的表达也有显着影响。结论大黄素通过抑制TLR3途径在手足口病CVB3介导的脑炎中发挥保护作用。
更新日期:2020-03-03
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