2. Academic Validation
  3. Inhibition of cGAS ameliorates acute lung injury triggered by zinc oxide nanoparticles

Inhibition of cGAS ameliorates acute lung injury triggered by zinc oxide nanoparticles

  • Toxicol Lett. 2022 Nov 8;S0378-4274(22)01779-9. doi: 10.1016/j.toxlet.2022.11.002.
Ziqi Jiang 1,  Yu Jiang 2,  Jingchuan Fan 3,  Jun Zhang 1,  Ge Xu 1,  Yinzhen Fan 1,  Liyu Zhang 3,  Xia Qin 4,  Xuejun Jiang 5,  Lejiao Mao 1,  Gang Liu 6,  Chengzhi Chen 7,  Zhen Zou 8
Affiliations

Affiliations

  • 1 Molecular Biology Laboratory of Respiratory Disease, Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, People's Republic of China.
  • 2 Department of Respiratory Medicine, The University‑Town Hospital of Chongqing Medical University, Chongqing 401331, People's Republic of China.
  • 3 Department of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
  • 4 Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China.
  • 5 Center of Experimental Teaching for Public Health, Experimental Teaching and Management Center, Chongqing Medical University, Chongqing, People's Republic of China.
  • 6 Department of Emergency, The University‑Town Hospital of Chongqing Medical University, Chongqing 401331, People's Republic of China. Electronic address: [email protected].
  • 7 Department of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing 400016, People's Republic of China; Research Center for Environment and Human Health, School of Public Health, Chongqing Medical University, Chongqing 400016, People's Republic of China. Electronic address: [email protected].
  • 8 Molecular Biology Laboratory of Respiratory Disease, Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, People's Republic of China; Research Center for Environment and Human Health, School of Public Health, Chongqing Medical University, Chongqing 400016, People's Republic of China. Electronic address: [email protected].
PMID: 36368621 DOI: 10.1016/j.toxlet.2022.11.002
Abstract

Purpose: Zinc oxide nanoparticles (ZnONPs) have been widely used in various industrial and biomedical fields. Occupational or accidental inhalation exposure to ZnONPs might lead to acute lung injury (ALI). Cyclic GMP-AMP Synthase (cGAS) and stimulator of interferon genes (STING) are critical for the initiation and expansion of inflammation and contribute to tissue injury; however, the role and mechanism of the cGAS-STING pathway in ALI-induced by ZnONPs are unclear.

Methods: Male C57BL/6J mice were intratracheally injected with ZnONPs (0.6mg/kg) or mock. The mice were euthanized and the degree of lung injury was determined 3 days after the instillation of ZnONPs. The BEAS-2B cell line was used as a cell model to investigate the cytotoxicity of ZnONPs in vitro.

Results: We found that ZnONPs inhalation induced ALI in mice, manifested by exacerbated lung pathological changes, mitochondrial damage, oxidative stress and inflammation. Interestingly, cGAS and STING were activated in the lung tissues of the mice and BEAS-2B lung epithelial cells treated with ZnONPs. More importantly, we illustrated that the cGAS inhibitor RU.521 inhibited the activation of the cGAS-STING pathway, further decreased oxidative stress and inflammation, and led to ameliorated lung injury in mice treated with ZnONPs.

Conclusion: This study demonstrated that ZnONPs trigger the activation of the cGAS-STING pathway, which plays an important role in ZnONPs-induced ALI. Inhibition of cGAS with RU.521 mitigates the oxidative stress induced by ZnONPs, suggesting that targeting the cGAS-STING pathway may be a feasible strategy to ameliorate the pulmonary injury caused by nanoparticles.

Keywords

RU.521; acute lung injury; cGAS; inflammation; zinc oxide nanoparticles.

Figures
Products