Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL/6 mice
Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL/6 mice
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中和白细胞介素 17A 可延缓 C57BL/6 小鼠二氧化硅诱导的肺部炎症和纤维化的进展
DOI：
10.1016/j.taap.2013.11.012
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发表时间：
2014-02-15
影响因子：
3.8
通讯作者：
Chen, Jie
中科院分区：
文献类型：
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作者：
Chen, Ying;Li, Cuiying;Chen, Jie
二氧化硅暴露可导致肺部炎症和纤维化，称为硅肺。白细胞介素-17A（IL-17 A）和Th 17细胞在控制炎症性疾病中起关键作用。然而，IL-17 A和Th 17细胞在二氧化硅诱导的炎症和纤维化的进展中的作用知之甚少。本研究探讨了IL-17 A对二氧化硅诱导的炎症和纤维化的影响。我们使用抗小鼠IL-17 A抗体建立IL-17 A中和的小鼠模型，并将小鼠暴露于二氧化硅中以建立实验性硅肺模型。我们发现，IL-17 A中和延迟中性粒细胞的积累和二氧化硅诱导的肺部炎症和纤维化的进展。IL-17 A中和作用降低了CD 4 + T细胞中Th 17的百分比，降低了IL-6和IL-1 β的表达，并在二氧化硅诱导的炎症的早期阶段增加了T细胞。IL-17 A的中和作用延迟二氧化硅诱导的Th 1/Th 2免疫和自身免疫应答。这些结果表明，IL-17 A中和作用使早期二氧化硅诱导的肺部炎症恶化，并延迟二氧化硅诱导的肺部炎症和纤维化的进展。在二氧化硅诱导的炎症的早期阶段，IL-17 A的中和通过降低IL-6和/或IL-1 β和增加Tcl 3抑制Th 17细胞的发育。IL-17 A的中和作用也延迟了二氧化硅诱导的肺部炎症和纤维化过程中的Th 1/Th 2免疫应答。IL-17 A可能在二氧化硅诱导的炎症反应的早期阶段起关键作用，并可能介导Th免疫应答以影响二氧化硅诱导的小鼠肺炎症和纤维化。(C)2013 Elsevier Inc. All rights reserved.
Silica exposure can cause lung inflammation and fibrosis, known as silicosis. Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling inflammatory diseases. However, the roles of IL-17A and Th17 cells in the progress of silica-induced inflammation and fibrosis are poorly understood. This study explored the effects of IL-17A on silica-induced inflammation and fibrosis. We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice model, and mice were exposed to silica to establish an experimental silicosis model. We showed that IL-17A neutralization delayed neutrophil accumulation and progression of silica-induced lung inflammation and fibrosis. IL-17A neutralization reduced the percentage of Th17 in CD4+ T cells, decreased IL-6 and IL-1 beta expression, and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and autoimmune responses. These results suggest that IL-17A neutralization alleviates early stage silica-induced lung inflammation and delays progression of silica-induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17 cell development by decreasing IL-6 and/or IL-1 beta and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A also delayed the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis. IL-17A may play a pivotal role in the early phase of silica-induced inflammation and may mediate the Th immune response to influence silica-induced lung inflammation and fibrosis in mice. (C) 2013 Elsevier Inc. All rights reserved.