Cytosolic Sensors of Viral RNA Are Involved in the Production of Interleukin-6 via Toll-Like Receptor 3 Signaling in Human Glomerular Endothelial Cells
Cytosolic Sensors of Viral RNA Are Involved in the Production of Interleukin-6 via Toll-Like Receptor 3 Signaling in Human Glomerular Endothelial Cells
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DOI：
10.1159/000498837
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发表时间：
2019-01-01
影响因子：
2.8
通讯作者：
Tanaka, Hiroshi
中科院分区：
文献类型：
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作者：
Liu, Qiang;Imaizumi, Tadaatsu;Tanaka, Hiroshi
背景/目标：残余肾细胞产生白细胞介素-6（IL-6）的失调可能在肾小球肾炎（GN）的发生发展中起关键作用。鉴于Toll样受体3（TLR 3）信号转导与某些形式的GN的发病机制有关，我们在培养的正常人肾小球内皮细胞（GECs）中检测了激活的TLR 3介导的IL-6信号转导。研究方法：我们处理GECs与聚肌胞苷酸（聚IC），一个真正的双链RNA，并分析了IL-6的表达和胞质病毒RNA传感器视黄酸诱导基因-I（RIG-I）和黑色素瘤分化相关基因5（MDA 5）使用逆转录定量实时聚合酶链反应，蛋白质印迹和酶联免疫吸附试验。为了进一步阐明聚IC对该信号传导途径的影响，我们使细胞经受针对TLR 3、干扰素（IFN）-β、RIG-I和MDA 5的小干扰RNA（siRNA）。结果：发现poly IC通过TLR 3/IFN-β信号通路诱导GECs表达RIG-I、MDA 5和IL-6。siRNA实验显示，MDA 5和RIG-1都参与了poly IC诱导的IL-6表达，MDA 5位于RIG-1的上游。结论：有趣的是，发现病毒RNA的胞质传感器通过TLR 3信号在GECs中参与IL-6的产生。由于病毒和“假病毒”感染导致的TLR 3/IFN-β/MDA 5/RIG-I/IL-6轴的区域活化涉及GEC中的先天免疫和炎性反应。我们相信这种信号通路在某些形式的GN的发展中也起着关键作用。(C)2019作者（S）由S发布。Karger AG，巴塞尔
Background/Aims: Dysregulation of interleukin-6 (IL-6) production in residual renal cells may play a pivotal role in the development of glomerulonephritis (GN). Given that Toll-like receptor 3 (TLR3) signaling has been implicated in the pathogenesis of some forms of GN, we examined activated TLR3-mediated IL-6 signaling in cultured normal human glomerular endothelial cells (GECs). Methods: We treated GECs with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, and analyzed the expression of IL-6 and the cytosolic viral RNA sensors retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) using reverse transcription quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assays. To further elucidate the effects of poly IC on this signaling pathway, we subjected the cells to small interfering RNA (siRNA) against TLR3, interferon (IFN)-ss, RIG-I, and MDA5. Results: We found that poly IC induced the expression of RIG-I, MDA5 and IL-6 via TLR3/IFN-ss signaling in GECs. siRNA experiments revealed that both MDA5 and RIG-I were involved in the poly IC-induced expression of IL-6, with MDA5 being upstream of RIG-I. Conclusion: Interestingly, cytosolic sensors of viral RNA were found to be involved in IL-6 production via TLR3 signaling in GECs. Regional activation of TLR3/IFN-ss/MDA5/RIG-I/IL-6 axis due to viral and "pseudoviral" infections is involved in innate immunity and inflammatory reactions in GECs. We believe this signaling pathway also plays a pivotal role in the development of some forms of GN. (C) 2019 The Author(s) Published by S. Karger AG, Basel