TY - JOUR
T1 - Role of Nrf2 in inflammatory response in lung of mice exposed to zinc oxide nanoparticles
AU - Sehsah, Radwa
AU - Wu, Wenting
AU - Ichihara, Sahoko
AU - Hashimoto, Naozumi
AU - Hasegawa, Yoshinori
AU - Zong, Cai
AU - Itoh, Ken
AU - Yamamoto, Masayuki
AU - Elsayed, Ahmed Ali
AU - El-Bestar, Soheir
AU - Kamel, Emily
AU - Ichihara, Gaku
N1 - Publisher Copyright:
© 2019 The Author(s).
PY - 2019/12/16
Y1 - 2019/12/16
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85076704778
UR - https://www.scopus.com/pages/publications/85076704778#tab=citedBy
U2 - 10.1186/s12989-019-0328-y
DO - 10.1186/s12989-019-0328-y
M3 - Article
C2 - 31842927
AN - SCOPUS:85076704778
SN - 1743-8977
VL - 16
JO - Particle and Fibre Toxicology
JF - Particle and Fibre Toxicology
IS - 1
M1 - 47
ER -