Toll-like receptor 3 signaling contributes to the expression of a neutrophil chemoattractant, CXCL1 in human mesangial cells
Toll-like receptor 3 signaling contributes to the expression of a neutrophil chemoattractant, CXCL1 in human mesangial cells
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DOI：
10.1007/s10157-014-1060-4
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发表时间：
2015-10-01
影响因子：
2.3
通讯作者：
Tanaka, Hiroshi
中科院分区：
文献类型：
--
作者：
Imaizumi, Tadaatsu;Aizawa, Tomomi;Tanaka, Hiroshi
肾小球系膜促炎症因子/细胞因子通过先天免疫的表达在肾炎的发病机制中起着关键作用。CXCL1/Groα是一种强中性粒细胞趋化因子，在局部炎症反应中发挥重要作用。然而，病毒或“假病毒”免疫诱导系膜细胞CXCL1表达的具体信号转导机制尚不清楚。我们用正品双链RNA多聚肌苷多胞苷(PolyIC)处理培养的人系膜细胞(MC)，用逆转录聚合酶链式反应(RT-PCR)、实时定量RT-PCR和酶联免疫吸附试验分析CXCL1的表达。为了阐明Poly IC诱导CXCL1表达的信号通路，我们对Toll样受体(TLR)3、视黄酸诱导基因I(RIG-I)、黑色素瘤分化相关基因5(MDA5)、干扰素(干扰素)-β、核因子(NF)-kappa B p65和干扰素调节因子(IRF)3进行了RNA干扰。我们还进行了免疫荧光研究，检测了狼疮性肾炎(LN)和IgA肾病(IgAN)患者肾小球系膜CXCL1的表达。在这种情况下，未发现RIG-I和MDA5参与系膜细胞CXCL1的表达，而核因子-kappa B、IRF3和干扰素-β均未参与。地塞米松可抑制聚IC对CXCL1的诱导作用。肾小球CXCL1在LN患者的肾活检标本中有较强的表达，而在IgAN患者的标本中仅有少量染色。TLR3信号也参与了肾小球系膜细胞中CXCL1的表达。这些观察进一步支持了病毒和“假病毒”免疫在炎症性肾脏疾病的发病机制中的意义，尤其是在LN中。
Mesangial proinflammatory chemokine/cytokine expressions via innate immunity play a pivotal role in the pathogenesis of glomerulonephritis. CXCL1/GRO alpha is a strong neutrophil chemoattractant cytokine and reportedly plays an important role in regional inflammatory reactions. However, detailed signaling of mesangial CXCL1 expression induced by viral or "pseudoviral" immunity remains to be determined.We treated normal human mesangial cells (MCs) in culture with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, and analyzed the expression of CXCL1 by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative RT-PCR and enzyme-linked immunosorbent assay. To elucidate the poly IC-induced signaling pathway for CXCL1 expression, we subjected the cells to RNA interference against Toll-like receptor (TLR) 3, retinoic acid-inducible gene-I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), interferon (IFN)-beta, nuclear factor (NF)-kappa B p65 and IFN regulatory factor (IRF) 3. We also conducted an immunofluorescence study to examine mesangial CXCL1 expression in biopsy specimens from patients with lupus nephritis (LN) and IgA nephropathy (IgAN).We found that activation of TLR3 signaling could induce the expression of CXCL1 in MCs. NF-kappa B, IRF3 and IFN-beta, but neither RIG-I nor MDA5, were found to be involved in mesangial CXCL1 expression in this setting. Induction of CXCL1 by poly IC was inhibited by pretreatment of cells with dexamethasone. Intense glomerular CXCL1 expression was observed in biopsy specimens from patients with LN, whereas only a trace staining occurred in specimens from patients with IgAN.TLR3 signaling also contributes to the CXCL1 expression in MCs. These observations further support the implication of viral and "pseudoviral" immunity in the pathogenesis of inflammatory renal diseases, especially in LN.