Zinc oxide nanoparticles (ZnO-NPs) are widely used in many industrial sectors and previous studies have reported that exposure of the lungs to ZnO-NPs induces both acute and/or chronic pulmonary inflammation, but the exact mechanism underlying such response remains elusive. This study investigated the role of nuclear factor-erythroid 2-related factor (Nrf2) in pulmonary inflammation induced by exposure to ZnO-NPs using Nrf2 null (Nrf2−/−) mice. Twenty-four male Nrf2−/− mice and thirty male wild type C57BL/6 J mice were divided into three groups of eight and ten each respectively, and exposed once to ZnO-NPs at 0, 10, 30 μg/mouse by pharyngeal aspiration. At 14 days after the exposure to ZnO-NPs, bronchoalveolar lavage fluid (BALF) and lungs were collected to quantify protein level and the number of inflammatory cells. The mRNA levels of Nrf2-dependent antioxidant enzymes and inflammatory cytokines in lung tissue were measured. Exposure to ZnO-NPs dose-dependently increased the number of total cells, macrophages, lymphocytes and eosinophils in BALF both in Nrf2−/− mice and wild type mice, but the magnitude of increase was significantly higher in Nrf2−/− mice than wild type mice. The number of neutrophils in BALF increased in Nrf2−/− mice, being accompanied by marginal trend of increase in mRNA expression of MIP-2, neutrophil chemoattractant, but such changes were not observed in wild type mice. Exposure to ZnO-NPs did not dose-dependently increase mRNA level of Nrf2-dependent antioxidant enzymes both in Nrf2−/− mice and wild type mice. Pharyngeal aspiration of ZnO-NPs induced infiltration of inflammatory cells in the lung of mice, but minimally induced Nrf2-dependent antioxidant enzymes. The results suggest that Nrf2 play a role in negative regulation on ZnO-NP exposure-induced neutrophil migration, but does not demonstrate that the regulation is through suppression of oxidative stress.

中文翻译：

---

Nrf2在暴露于氧化锌纳米粒子的小鼠肺部炎症反应中的作用。

氧化锌纳米颗粒（ZnO-NPs）被广泛用于许多工业领域，先前的研究已经报道了将肺暴露于ZnO-NPs会引起急性和/或慢性肺部炎症，但是这种反应的确切机制仍然难以捉摸。这项研究使用Nrf2无效（Nrf2-/-）小鼠研究了核因子-类胡萝卜素2相关因子（Nrf2）在暴露于ZnO-NPs引起的肺部炎症中的作用。将24只雄性Nrf2-/-小鼠和30只雄性野生型C57BL / 6 J小鼠分为三组，每组分别为八和十只，并通过咽抽吸以0、10、30μg/小鼠一次暴露于ZnO-NP。 。暴露于ZnO-NPs后第14天，收集支气管肺泡灌洗液（BALF）和肺以定量蛋白质水平和炎性细胞数量。测量了肺组织中Nrf2依赖的抗氧化酶和炎症细胞因子的mRNA水平。在Nrf2-/-小鼠和野生型小鼠中，暴露于ZnO-NPs均会剂量依赖性地增加BALF中的总细胞，巨噬细胞，淋巴细胞和嗜酸性粒细胞的数量，但Nrf2-/-小鼠中的增加幅度明显高于野生型型小鼠。Nrf2-/-小鼠BALF中嗜中性粒细胞的数量增加，伴随着嗜中性粒细胞趋化因子MIP-2 mRNA表达增加的边缘趋势，但在野生型小鼠中未观察到这种变化。在Nrf2-/-小鼠和野生型小鼠中，暴露于ZnO-NPs均未剂量依赖性地增加Nrf2依赖的抗氧化酶的mRNA水平。ZnO-NPs的咽部吸入引起小鼠肺部炎性细胞的浸润，但最低程度地诱导了Nrf2依赖的抗氧化酶。结果表明，Nrf2在ZnO-NP暴露诱导的中性粒细胞迁移的负调控中发挥作用，但没有证明该调控是通过抑制氧化应激而实现的。