Qiao Yamei, Liang Xiao, Yan Yingjie, Lu Yake, Zhang Di, Yao Wu, Wu Weidong, Yan Zhen
Department of Occupational and Environmental Health Sciences, College of Public Health, Zhengzhou University, Zhengzhou, China.
Department of Occupational and Environmental Health Sciences, School of Public Health, Xinxiang Medical University, Xinxiang, China.
Front Physiol. 2018 Mar 13;9:217. doi: 10.3389/fphys.2018.00217. eCollection 2018.
It has been previously shown that inhaled zinc oxide nanoparticles (ZnO-NPs) can modulate inflammation. MicroRNAs (miRNAs) enclosed in exosomes have been identified as an important signature for inflammatory responses. However, the role of exosomal miRNAs during pathogenic inflammation has not been investigated. Healthy rats were exposed to ZnO-NPs (41.7 nm; 2, 4, and 8 mg/kg) or saline (control) via oropharyngeal aspiration. ZnO-NPs induced significant increases in the serum levels of interleukin 8 (IL-8), interleukin-1 beta (IL-1β), and tumor necrosis factor α (TNF-α), and elevated the number of cells and the percentage of neutrophils in the blood. Moreover, exposure to ZnO-NPs increased the levels of lactate dehydrogenase (LDH) activity and total protein in bronchoalveolar lavage fluid (BALF). Differential profiling of miRNAs in isolated serum exosomes revealed that 16 miRNAs were up-regulated and 7 down-regulated in ZnO-NP-treated rats compared with the controls. Functional and pathway analysis indicated that miRNAs may participate in inflammation directly and indirectly through protein and vesicle-mediated transport or regulation of IL-1, oxidative stress, apoptosis, and autophagy. These results suggest that miRNAs in serum exosomes are involved in pulmonary neutrophilic inflammation induced by ZnO-NPs.
先前的研究表明，吸入的氧化锌纳米颗粒（ZnO-NPs）可调节炎症。外泌体中包含的微小RNA（miRNAs）已被确定为炎症反应的重要标志。然而，外泌体miRNAs在致病性炎症中的作用尚未得到研究。通过口咽吸入法，将健康大鼠暴露于ZnO-NPs（41.7纳米；2、4和8毫克/千克）或生理盐水（对照）中。ZnO-NPs导致血清白细胞介素8（IL-8）、白细胞介素-1β（IL-1β）和肿瘤坏死因子α（TNF-α）水平显著升高，并增加了血液中的细胞数量和中性粒细胞百分比。此外，暴露于ZnO-NPs会增加支气管肺泡灌洗液（BALF）中乳酸脱氢酶（LDH）活性和总蛋白水平。对分离的血清外泌体中miRNAs的差异分析显示，与对照组相比，ZnO-NP处理的大鼠中有16种miRNAs上调，7种下调。功能和通路分析表明，miRNAs可能通过蛋白质和囊泡介导的转运或对IL-1、氧化应激、细胞凋亡和自噬的调节直接或间接参与炎症反应。这些结果表明，血清外泌体中的miRNAs参与了ZnO-NPs诱导的肺部中性粒细胞炎症。
