Interleukin-17A participates in podocyte injury by inducing IL-1β secretion through ROS-NLRP3 inflammasome-caspase-1 pathway
Interleukin-17A participates in podocyte injury by inducing IL-1β secretion through ROS-NLRP3 inflammasome-caspase-1 pathway
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Interleukin-17A 通过 ROS-NLRP3 炎性体-caspase-1 途径诱导 IL-1β 分泌参与足细胞损伤
DOI：
10.1111/sji.12645
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发表时间：
2018-04-01
影响因子：
3.7
通讯作者：
Li, Q.
中科院分区：
文献类型：
--
作者：
Yan, J.;Li, Y.;Li, Q.
研究表明，Th17/IL-17A轴在肾脏疾病的发病机制中起重要作用。此前，我们也表明IL-17A可能在原发性肾病综合征的发病机制中发挥作用，但其潜在机制尚不清楚(S)。本研究旨在探讨IL-17A诱导足细胞损伤的分子机制。本研究通过免疫印迹和免疫荧光检测NLRP3炎性小体的激活和足细胞的形态。结果表明，足细胞持续表达IL-17A受体，IL-17A可激活足细胞中的NLRP3炎症体。IL-17A可使caspase-1活性和IL-1分泌增加。此外，IL-17A通过降低podocin的表达和增加desmin的表达来破坏足细胞的形态。阻断细胞内ROS或抑制caspase-1可阻止NLRP3炎症体的激活，从而恢复足细胞的形态。综上所述，这些结果提示，IL-17A通过激活NLRP3炎症体和IL-1的分泌而导致足细胞损伤，并参与破坏肾脏的滤过系统。
Studies show that the Th17/IL-17A axis plays an important role in the pathogenesis of kidney diseases. Previously, we also showed that IL-17A may play a role in the pathogenesis of primary nephrotic syndrome; however, the underlying mechanism(s) is unclear. The aim of this study was to explore the molecular mechanism of IL-17A-inducing podocyte injury invitro. In this study, the NLRP3 inflammasome activation and the morphology of podocytes were detected by Western blot and immunofluorescence. The results showed that podocytes persistently expressed IL-17A receptor and that NLRP3 inflammasome in these cells was activated upon exposure to IL-17A. Also, activity of caspase-1 and secretion of IL-1 increased in the presence of IL-17A. In addition, IL-17A disrupted podocyte morphology by decreasing expression of podocin and increasing expression of desmin. Blockade of intracellular ROS or inhibition of caspase-1 prevented activation of the NLRP3 inflammasome, thereby restoring podocyte morphology. Taken together, the results suggest that IL-17A induces podocyte injury by activating the NLRP3 inflammasome and IL-1 secretion and contributes to disruption of the kidney's filtration system.