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

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Abstract 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 maleNrf2−/−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 ofNrf2-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 inNrf2−/−mice and wild type mice, but the magnitude of increase was significantly higher inNrf2−/−mice than wild type mice. The number of neutrophils in BALF increased inNrf2−/−mice, being accompanied by marginal trend of increase in mRNA expression ofMIP-2, neutrophil chemoattractant, but such changes were not observed in wild type mice. Exposure to ZnO-NPs did not dose-dependently increase mRNA level ofNrf2-dependent antioxidant enzymes both inNrf2−/−mice and wild type mice. Conclusion Pharyngeal aspiration of ZnO-NPs induced infiltration of inflammatory cells in the lung of mice, but minimally inducedNrf2-dependent antioxidant enzymes. The results suggest thatNrf2play 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.

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