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猪圆环病毒 2 型通过 RIG-I/MDA-5/MAVS/JNK 信号通路上调猪髂动脉内皮细胞中内皮细胞衍生的白细胞介素-8 的产生。

Porcine circovirus type 2 upregulates endothelial-derived IL-8 production in porcine iliac artery endothelial cells via the RIG-I/MDA-5/MAVS/JNK signaling pathway.

机构信息

College of Animal Science and Technology, Beijing University of Agriculture, No. 7 Beinong Road, Beijing, 102206, Changping District, China.

Beijing Key Laboratory of TCVM, Beijing University of Agriculture, No. 7 Beinong Road, Beijing, 102206, Changping District, China.

出版信息

BMC Vet Res. 2020 Jul 29;16(1):265. doi: 10.1186/s12917-020-02486-1.

Abstract

BACKGROUND

Dysfunction of endothelial cells and vascular system is one of the most important pathological changes of porcine circovirus disease (PCVD) caused by porcine circovirus type 2 (PCV2). PCV2-infected endothelial cells can upregulate the production of endothelial-derived IL-8, which can inhibit the maturation of dendritic cells. Endothelial-derived IL-8 has different structural and biological characteristics compared with monocyte-derived IL-8. However, the mechanism of endothelial-derived IL-8 production is still unclear.

RESULTS

Key molecules of RIG-I-like signaling pathway RIG-I, MDA-5, MAVS and a key molecule of JNK signaling pathway c-Jun in PCV2-infected porcine iliac artery endothelial cells (PIECs) were upregulated significantly detected with quantitative PCR, Western blot and fluorescence confocal microscopy, while no significant changes were found in NF-κB signaling pathway. Meanwhile, the expression of endothelial-derived IL-8 was downregulated after RIG-I, MDA-5, or MAVS genes in PIECs were knocked down and PIECs were treated by JNK inhibitor.

CONCLUSIONS

PCV2 can activate RIG-I/MDA-5/MAVS/JNK signaling pathway to induce the production of endothelial-derived IL-8 in PIECs, which provides an insight into the further study of endothelial dysfunction and vascular system disorder caused by PCV2.

摘要

背景

内皮细胞和血管系统功能障碍是由猪圆环病毒 2 型(PCV2)引起的猪圆环病毒病(PCVD)的最重要的病理变化之一。PCV2 感染的内皮细胞可以上调内皮细胞衍生的白细胞介素-8(IL-8)的产生,这可以抑制树突状细胞的成熟。内皮细胞衍生的 IL-8 与单核细胞衍生的 IL-8 具有不同的结构和生物学特征。然而,内皮细胞衍生的 IL-8 产生的机制尚不清楚。

结果

通过定量 PCR、Western blot 和荧光共聚焦显微镜检测到,在 PCV2 感染的猪髂动脉内皮细胞(PIEC)中,RIG-I 样信号通路的关键分子 RIG-I、MDA-5、MAVS 和 JNK 信号通路的关键分子 c-Jun 显著上调,而 NF-κB 信号通路没有明显变化。同时,当 PIEC 中的 RIG-I、MDA-5 或 MAVS 基因被敲低或用 JNK 抑制剂处理时,内皮细胞衍生的 IL-8 的表达下调。

结论

PCV2 可以激活 RIG-I/MDA-5/MAVS/JNK 信号通路,诱导 PIEC 中内皮细胞衍生的 IL-8 的产生,这为进一步研究 PCV2 引起的内皮功能障碍和血管系统紊乱提供了思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44f4/7392700/49a2f4f917e7/12917_2020_2486_Fig1_HTML.jpg

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