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Background  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.    Methods  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.    Results  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.    Conclusion  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.

Role of Nrf2 in inflammatory response in lung of mice exposed to zinc oxide nanoparticles