Effect of Pulmonary Inflammation by Surface Functionalization of Zinc Oxide Nanoparticles

Jung, A Young; Kim, Sung-Hyun; Yang, Jun-Young; Jeong, Jayoung; Lee, Jong Kwon; Oh, Jae-Ho

doi:10.3390/toxics9120336

Cited by 7 publications

(5 citation statements)

References 38 publications

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“…A study of 3.3 ± 0.6 mg/m 3 nZnO (10 nm) inhalation exposure to mice for 13 weeks also caused an increase in macrophages in BALF and a moderate increase in IL-12 [ 35 ]. In line with our findings, another study of single inhalation exposure to 300 μg of nZnO (20 nm) in rats caused acute lung injury with granulocyte accumulation and also showed significantly increased proinflammatory IL-6 and TNF production to the BALF of rat lungs after intratracheal instillation of nZnO at 1 day [ 36 ]. Exposure of mice to 2, 6, and 18 μg of nZnO (12 ± 3 nm) by a single intratracheal instillation after 3 days caused a very strong inflammatory response and increase in neutrophils in BALF [ 37 ].…”

Section: Discussionsupporting

confidence: 88%

Transcriptomic Profiling the Effects of Airway Exposure of Zinc Oxide and Silver Nanoparticles in Mouse Lungs

Zhao

Wang

Ilves

et al. 2023

IJMS

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Consumers and manufacturers are exposed to nanosized zinc oxide (nZnO) and silver particles (nAg) via airways, but their biological effects are still not fully elucidated. To understand the immune effects, we exposed mice to 2, 10, or 50 μg of nZnO or nAg by oropharyngeal aspiration and analyzed the global gene expression profiles and immunopathological changes in the lungs after 1, 7, or 28 days. Our results show that the kinetics of responses varied in the lungs. Exposure to nZnO resulted in the highest accumulation of F4/80- and CD3-positive cells, and the largest number of differentially expressed genes (DEGs) were identified after day 1, while exposure to nAg caused peak responses at day 7. Additionally, nZnO mainly activated the innate immune responses leading to acute inflammation, whereas the nAg activated both innate and adaptive immune pathways, with long-lasting effects. This kinetic-profiling study provides an important data source to understand the cellular and molecular processes underlying nZnO- and nAg-induced transcriptomic changes, which lead to the characterization of the corresponding biological and toxicological effects of nZnO and nAg in the lungs. These findings could improve science-based hazard and risk assessment and the development of safe applications of engineered nanomaterials (ENMs), e.g., in biomedical applications.

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Section: Discussionsupporting

confidence: 88%

Transcriptomic Profiling the Effects of Airway Exposure of Zinc Oxide and Silver Nanoparticles in Mouse Lungs

Zhao

Wang

Ilves

et al. 2023

IJMS

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“…Genes involved in inflammation were found to be upregulated (more than a 20-fold increase) after ZnO MONP treatment in CA77 cells: Ccr5 and Zfp36l1 ( Figure 12 ). It is known that ZnO MONPs induce inflammation as reported many times, especially in mammalian cells [ 46 , 47 , 48 ]. Therefore, in CA77 cells, it appears that Ccr5 and Zfp361l upregulation in response to ZnO treatment takes place to promote inflammation.…”

Section: Discussionmentioning

confidence: 99%

Non-ROS-Mediated Cytotoxicity of ZnO and CuO in ML-1 and CA77 Thyroid Cancer Cell Lines

Peters

Weaver

Monahan

et al. 2023

IJMS

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Metal oxide nanoparticles (MONPs) are widely used in agriculture and food development but there is little understanding of how MONPs, including ZnO, CuO, TiO2, and SnO2, impact human health and the environment. Our growth assay revealed that none of these (up to 100 µg/mL) negatively affect viability in the budding yeast, Saccharomyces cerevisiae. In contrast, both human thyroid cancer cells (ML-1) and rat medullary thyroid cancer cells (CA77) displayed a significant reduction in cell viability with the treatment of CuO and ZnO. The production of reactive oxygen species (ROS) in these cell lines, when treated with CuO and ZnO, was found to be not significantly altered. However, levels of apoptosis with ZnO and CuO were increased, which led us to conclude that the decreased cell viability is mainly caused by non-ROS-mediated cell death. Consistently, data from our RNAseq studies identified differentially regulated pathways associated with inflammation, Wnt, and cadherin signaling across both cell lines, ML-1, and CA77, after ZnO or CuO MONP treatment. Results from gene studies further support non-ROS-mediated apoptosis being the main factor behind decreased cell viability. Together, these findings provide unique evidence that the apoptosis in response to treatment of CuO and ZnO in these thyroid cancer cells was not mainly due to oxidative stress, but to the alteration of a range of signal cascades that promotes cell death.

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“…The mice were divided into two groups, control group and Nano-ZnO treatment group. Mice in Nano-ZnO group were intranasally instilled with 50 mg/kg/day per mouse of Nano-ZnO and lungs were collected at day 7 after exposure based on previous study (Nazir et al 2019;Wu et al 2014;Jung, et al 2021). HE staining, TEM observation and Western blotting were used for detection of relative values.…”

Section: Exposure Of Mice To Nano-zno Particlesmentioning

confidence: 99%

Role of p53/circRNA0085439/Ku70 axis in DNA damage response in lung cells exposed to ZnO nanoparticles: Involvement of epigenetic regulation

et al. 2023

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Background Nano-Zinc oxide (Nano-ZnO) has been increasingly applied in agriculture, industry and biomedicine. However, the genotoxic effects of Nano-ZnO and the underlying mechanisms remain incompletely clear. Methods Human bronchial epithelial cell line (HBE) was used to observe the effects of Nano-ZnO on DNA damage repair-related proteins and epithelial mesenchymal transition (EMT) by Western blotting. Then, CRISPR/cas9-based technique was used to create p53 knockout (p53-KO) cell line. RNA-seq analysis was performed to uncover the circular RNA (circRNA) profile after Nano-ZnO treatment in p53-KO cells compared with p53 wild-type (p53-wt) cells. LC–MS/MS was used to discover the potential binding proteins of circRNA_0085439 in the p53 deficiency background after Nano-ZnO treatment. Nano-ZnO-induced DNA damage and EMT were also investigated in vivo by instillation of Nano-ZnO (50 µg/mouse). Results Nano-ZnO exposure caused DNA damage and EMT at both in vitro and in vivo background, which was reflected by increased DNA damage associated proteins such as ATM and ATR and γ H2AX. p53 expression increased at the early stage post Nano-ZnO treatment decreased later. RNA-seq assay showed a highest increase of circRNA_0085439 expression in p53-KO cells compared with the p53-wt cells after Nano-ZnO exposure. Silencing of p53 expression promoted its translocation of circRNA_0085439 from cytoplasm to nucleus leading to the formation of circRNA_0085439/Ku70 complex resulting in the decreased expression of Ku70 protein. In addition, increased EMT markers, N-cadherin and Vimentin, was observed in lung epithelial cells and in mouse lungs at day 7 after Nano-ZnO exposure. Conclusions This study unraveled the epigenetic mechanisms underlying Nano-ZnO-induced DNA damage and EMT. The effect of Nano-ZnO-induced DNA damage through p53/circRNA_0085439/Ku70 pathway likely contribute to Nano-ZnO-induced cell cytotoxicity and apoptosis. Our findings will provide information to further elucidate the molecular mechanisms of Nano-ZnO-induced cytotoxicity and genotoxicity.

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Effect of Pulmonary Inflammation by Surface Functionalization of Zinc Oxide Nanoparticles

Cited by 7 publications

References 38 publications

Transcriptomic Profiling the Effects of Airway Exposure of Zinc Oxide and Silver Nanoparticles in Mouse Lungs

Transcriptomic Profiling the Effects of Airway Exposure of Zinc Oxide and Silver Nanoparticles in Mouse Lungs

Non-ROS-Mediated Cytotoxicity of ZnO and CuO in ML-1 and CA77 Thyroid Cancer Cell Lines

Role of p53/circRNA0085439/Ku70 axis in DNA damage response in lung cells exposed to ZnO nanoparticles: Involvement of epigenetic regulation

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