Inflammation increases susceptibility of human small airway epithelial cells to pneumonic nanotoxicity
Exposure to inhaled anthropogenic nanomaterials (NM) with dimension <100 nm has been implicated in numerous adverse respiratory outcomes. Although studies have identified key NM physiochemical determinants of pneumonic nanotoxicity, the complex interactive and cumulative effects of NM exposure, e...
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sg-ntu-dr.10356-1552602022-03-07T05:44:51Z Inflammation increases susceptibility of human small airway epithelial cells to pneumonic nanotoxicity Wu, Zhuoran Shi, Pujiang Lim, Hong Kit Ma, Yiyuan Setyawati, Magdiel Inggrid Bitounis, Dimitrios Demokritou, Philip Ng, Kee Woei Tay, Chor Yong School of Materials Science and Engineering School of Biological Sciences Skin Research Institute of Singapore Environmental Chemistry and Materials Centre Nanyang Environment and Water Research Institute Engineering::Materials Cellular Adaptation Lung Inflammation Exposure to inhaled anthropogenic nanomaterials (NM) with dimension <100 nm has been implicated in numerous adverse respiratory outcomes. Although studies have identified key NM physiochemical determinants of pneumonic nanotoxicity, the complex interactive and cumulative effects of NM exposure, especially in individuals with preexisting inflammatory respiratory diseases, remain unclear. Herein, the susceptibility of primary human small airway epithelial cells (SAEC) exposed to a panel of reference NM, namely, CuO, ZnO, mild steel welding fume (MSWF), and nanofractions of copier center particles (Nano-CCP), is examined in normal and tumor necrosis factor alpha (TNF-α)-induced inflamed SAEC. Compared to normal SAEC, inflamed cells display an increased susceptibility to NM-induced cytotoxicity by 15-70% due to a higher basal level of intracellular reactive oxygen species (ROS). Among the NM screened, ZnO, CuO, and Nano-CCP are observed to trigger an overcompensatory response in normal SAEC, resulting in an increased tolerance against subsequent oxidative insults. However, the inflamed SAEC fails to adapt to the NM exposure due to an impaired nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated cytoprotective response. The findings reveal that susceptibility to pulmonary nanotoxicity is highly dependent on the interplay between NM properties and inflammation of the alveolar milieu. Nanyang Technological University Accepted version Z.W. and P.S. contributed equally to this work. The authors gratefully acknowledge support by the Nanyang Technological University—Harvard School of Public Health Initiative for Sustainable Nanotechnology (NTU-Harvard SusNano; NTU-Harvard Initiative for Sustainable Nanotechnology seed grant, reference number NTU-HSPH 18002). Engineered nanomaterials used in the research presented in this publication were synthesized, characterized, and provided by the Engineered Nanomaterials Resource and Coordination Core established at Harvard T. H. Chan School of Public Health (NIH grant # U24ES026946) as part of the Nanotechnology Health Implications Research (NHIR) Consortium. 2022-03-07T05:44:50Z 2022-03-07T05:44:50Z 2020 Journal Article Wu, Z., Shi, P., Lim, H. K., Ma, Y., Setyawati, M. I., Bitounis, D., Demokritou, P., Ng, K. W. & Tay, C. Y. (2020). Inflammation increases susceptibility of human small airway epithelial cells to pneumonic nanotoxicity. Small, 16(21), 2000963-. https://dx.doi.org/10.1002/smll.202000963 1613-6810 https://hdl.handle.net/10356/155260 10.1002/smll.202000963 32338442 2-s2.0-85084126971 21 16 2000963 en NTU-HSPH18002 Small © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. All rights reserved. |
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Engineering::Materials Cellular Adaptation Lung Inflammation Wu, Zhuoran Shi, Pujiang Lim, Hong Kit Ma, Yiyuan Setyawati, Magdiel Inggrid Bitounis, Dimitrios Demokritou, Philip Ng, Kee Woei Tay, Chor Yong Inflammation increases susceptibility of human small airway epithelial cells to pneumonic nanotoxicity |
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Exposure to inhaled anthropogenic nanomaterials (NM) with dimension <100 nm has been implicated in numerous adverse respiratory outcomes. Although studies have identified key NM physiochemical determinants of pneumonic nanotoxicity, the complex interactive and cumulative effects of NM exposure, especially in individuals with preexisting inflammatory respiratory diseases, remain unclear. Herein, the susceptibility of primary human small airway epithelial cells (SAEC) exposed to a panel of reference NM, namely, CuO, ZnO, mild steel welding fume (MSWF), and nanofractions of copier center particles (Nano-CCP), is examined in normal and tumor necrosis factor alpha (TNF-α)-induced inflamed SAEC. Compared to normal SAEC, inflamed cells display an increased susceptibility to NM-induced cytotoxicity by 15-70% due to a higher basal level of intracellular reactive oxygen species (ROS). Among the NM screened, ZnO, CuO, and Nano-CCP are observed to trigger an overcompensatory response in normal SAEC, resulting in an increased tolerance against subsequent oxidative insults. However, the inflamed SAEC fails to adapt to the NM exposure due to an impaired nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated cytoprotective response. The findings reveal that susceptibility to pulmonary nanotoxicity is highly dependent on the interplay between NM properties and inflammation of the alveolar milieu. |
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School of Materials Science and Engineering |
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School of Materials Science and Engineering Wu, Zhuoran Shi, Pujiang Lim, Hong Kit Ma, Yiyuan Setyawati, Magdiel Inggrid Bitounis, Dimitrios Demokritou, Philip Ng, Kee Woei Tay, Chor Yong |
format |
Article |
author |
Wu, Zhuoran Shi, Pujiang Lim, Hong Kit Ma, Yiyuan Setyawati, Magdiel Inggrid Bitounis, Dimitrios Demokritou, Philip Ng, Kee Woei Tay, Chor Yong |
author_sort |
Wu, Zhuoran |
title |
Inflammation increases susceptibility of human small airway epithelial cells to pneumonic nanotoxicity |
title_short |
Inflammation increases susceptibility of human small airway epithelial cells to pneumonic nanotoxicity |
title_full |
Inflammation increases susceptibility of human small airway epithelial cells to pneumonic nanotoxicity |
title_fullStr |
Inflammation increases susceptibility of human small airway epithelial cells to pneumonic nanotoxicity |
title_full_unstemmed |
Inflammation increases susceptibility of human small airway epithelial cells to pneumonic nanotoxicity |
title_sort |
inflammation increases susceptibility of human small airway epithelial cells to pneumonic nanotoxicity |
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2022 |
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https://hdl.handle.net/10356/155260 |
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