Interferon (IFN)-Induced Protein 35 (IFI35), a Type I Interferon-Dependent Transcript, Upregulates Inflammatory Signaling Pathways by Activating Toll-Like Receptor 3 in Human Mesangial Cells
Interferon (IFN)-Induced Protein 35 (IFI35), a Type I Interferon-Dependent Transcript, Upregulates Inflammatory Signaling Pathways by Activating Toll-Like Receptor 3 in Human Mesangial Cells
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DOI：
10.1159/000447932
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发表时间：
2016-01-01
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：
Imaizumi, Tadaatsu;Yano, Chikashi;Tanaka, Hiroshi
背景/目的：Toll 样受体 3 (TLR3) 信号传导的激活以及 I 型干扰素 (IFN) 的表达对于肾系膜细胞 (MC) 的抗病毒和“假病毒”免疫反应至关重要。这些反应可能与慢性肾脏病（CKD）的发病机制有关。然而，IFN 诱导的 35 kDa 蛋白 35 (IFI35)（一种 I 型 IFN 依赖性转录物）在肾小球炎症中的作用尚不清楚。在这里，我们的目的是研究 IFI35 在 MC 中 IFN-β/视黄酸诱导基因-I (RIG-I)/CCL5 和 IFN-β/黑色素瘤分化相关基因 5 (MDA5)/CXCL10 轴中的表达和作用。方法：我们用聚肌苷-聚胞苷酸（poly IC）（一种真正的双链RNA）处理人MC，然后通过逆转录聚合酶链反应和蛋白质印迹分析IFI35的表达。为了检查 IFI35 表达的调节，我们对 MC 进行了针对 IFN-β、RIG-I 和 MDA5 的 RNA 干扰 (siRNA)。结果：poly IC 激活 TLR3 诱导 MC 中 IFI35 表达。针对 IFN-β 的 siRNA 抑制聚 IC 诱导的 IFI35 表达。 IFI35 的敲低导致多聚 IC 诱导的 RIG-I 和 MDA5 蛋白减少，以及 CCL5 和 CXCL10 mRNA 和蛋白表达减少。然而，它不影响磷酸化信号转导子或转录激活子（STAT）1蛋白或RIG-I和MDA5的mRNA水平的表达。结论：IFI35的区域表达及其失调可能参与CKD肾小球炎症的发病机制。 (C) 2016 作者由巴塞尔 S. Karger AG 出版
Background/Aims: Activation of Toll-like receptor 3 (TLR3) signaling followed by type I interferon (IFN) expression is crucial in antiviral and "pseudoviral" immune reactions in renal mesangial cells (MCs). These reactions are probably involved in the pathogenesis of chronic kidney disease (CKD). However, the role of IFN-induced 35-kDa protein 35 (IFI35), a type I IFN-dependent transcript, in glomerular inflammation is unclear. Here, we aimed to investigate the expression and the role of IFI35 in IFN-beta/retinoic acid-inducible gene-I (RIG-I)/CCL5 and IFN-beta/melanoma differentiation-associated gene 5 (MDA5)/CXCL10 axes in MCs. Methods: We treated human MCs with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, then analysed the IFI35 expression by reverse transcription-polymerase chain reaction and western blotting. To examine the regulation of IFI35 expression, we subjected MCs to RNA interference (siRNA) against IFN-beta, RIG-I, and MDA5. Results: Activation of TLR3 by poly IC induces the IFI35 expression in MCs. siRNA against IFN-beta inhibited poly IC-induced IFI35 expression. Knockdown of IFI35 resulted in a decrease of poly IC-induced RIG-I and MDA5 protein as well as decreased CCL5 and CXCL10 mRNA and protein expression. However, it did not affect the expression of none of phosphorylated signal transducers or activator of transcription (STAT) 1 protein, or RIG-I and MDA5 in mRNA levels. Conclusion: Regional expression of IFI35 and its dysregulation may be involved in the pathogenesis of glomerular inflammation in CKD. (C) 2016 The Author(s) Published by S. Karger AG, Basel