Polyinosinic-Polycytidylic Acid Induces the Expression of Interferon-Stimulated Gene 20 in Mesangial Cells

Polyinosinic-Polycytidylic Acid Induces the Expression of Interferon-Stimulated Gene 20 in Mesangial Cells
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DOI:
10.1159/000328923
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发表时间:
2011-01-01
影响因子:
--
通讯作者:
Satoh, Kei
Satoh, Kei
中科院分区:
其他
文献类型:
--
作者:
Imaizumi, Tadaatsu;Tanaka, Hiroshi;Satoh, Kei

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背景/目的:干扰素刺激基因20(ISG20)是一种针对单链RNA的3‘-5’外切酶,参与宿主对RNA病毒的防御反应。ISG20在肾小球系膜细胞中的表达和作用尚未见报道。方法:培养正常人肾小球系膜细胞,用模拟病毒感染的双链RNA多聚肌苷多胞苷(Poly(I:C))处理细胞。检测Toll样受体3(TLR3)或干扰素-β的RNA干扰对ISG20表达的影响。对干扰素-β受体或抗炎类固醇激素地塞米松受体的封闭抗体的效果也进行了检测。结果:Poly(I:C)处理细胞后可诱导ISG20的表达。TLR3、干扰素调节因子3(IRF3)或干扰素-β均可抑制聚(I:C)诱导的ISG20的表达。阻断干扰素-β受体可抑制ISG20的表达,过表达干扰素-β可增强ISG20的表达。地塞米松可抑制聚(I:C)诱导的干扰素-β和ISG20的表达。将聚(I:C)或5‘-三磷酸单链RNA作为阳离子脂复合体转染系膜细胞,也可诱导ISG20的表达,这一作用可被维甲酸诱导基因-I(RIG-I)抑制。结论:Poly(I:C)可诱导系膜细胞表达ISG20。ISG20可能参与肾小球系膜细胞的抗病毒反应。TLR3、IRF3和从头合成的干扰素-β可能介导Poly(I:C)诱导的ISG20表达,RIG-I可能介导Poly(I:C)/阳离子脂复合物诱导的ISG20表达。版权所有(C)2011 S.Karger AG,巴塞尔
Background/Aims: Interferon (IFN)-stimulated gene 20 (ISG20) is a 3'-to-5' exonuclease specific for single-stranded RNA and involved in host defense reactions against RNA viruses. The expression and the role of ISG20 in mesangial cells have not been reported. Methods: Normal human mesangial cells were cultured and treated with polyinosinic-polycytidylic acid (poly (I:C)), an authentic double-stranded RNA which mimics viral infection to cells. The effect of RNA interference of Toll-like receptor 3 (TLR3) or IFN-beta on the ISG20 expression was examined. The effect of a blocking antibody against the receptor for IFN-beta or anti-inflammatory steroid dexamethasone was also examined. Results: Treatment of cells with poly (I:C) induced the expression of ISG20. The poly (I:C)-induced expression of ISG20 was inhibited by knockdown of TLR3, IFN regulatery factor 3 (IRF3) or IFN-beta. Blocking of the receptor for IFN-beta suppressed and overexpression of IFN-beta enhanced ISG20 expression. The poly (I:C)-induced expressions of IFN-beta and ISG20 were inhibited by dexamethasone. Transfection of mesangial cells with poly (I:C) or 5'-triphosphate single-stranded RNA as a complex with cationic lipid also induced the expression of ISG20, and this was inhibited by knockdown of retinoic acid-inducible gene-I (RIG-I). Conclusion: Poly (I:C) induces the expression of ISG20 in mesangial cells. ISG20 may be involved in anti-viral reactions in renal mesangial cells. TLR3, IRF3 and de novo synthesized IFN-beta may mediate the poly (I:C)-induced expression of ISG20, and RIG-I may mediate ISG20 expression induced by poly (I:C)/cationic lipid complex. Copyright (C) 2011 S. Karger AG, Basel