A missing jigsaw within the hygiene hypothesis: low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection
The rising occurrence of allergic asthma in early life across industrialized countries suggests that environmental factors play a crucial role in determining asthma susceptibility and severity. While prior exposure to microbial lipopolysaccharides (LPSs) has been found to offer protection against al...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Online Access: | https://hdl.handle.net/10356/173165 |
| _version_ | 1811680034030616576 |
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| author | Wang, Mengjing Qu, Jing Yang, Junjie Zhang, Tian Tan, Wei Ren Liao, Shumin Chen, Xing Liu, Yingzi Long, Xiang Li, Xue Xia, Yun Tan, Nguan Soon Li, Liang Fang, Mingliang |
| author2 | School of Civil and Environmental Engineering |
| author_facet | School of Civil and Environmental Engineering Wang, Mengjing Qu, Jing Yang, Junjie Zhang, Tian Tan, Wei Ren Liao, Shumin Chen, Xing Liu, Yingzi Long, Xiang Li, Xue Xia, Yun Tan, Nguan Soon Li, Liang Fang, Mingliang |
| author_sort | Wang, Mengjing |
| collection | NTU |
| description | The rising occurrence of allergic asthma in early life across industrialized countries suggests that environmental factors play a crucial role in determining asthma susceptibility and severity. While prior exposure to microbial lipopolysaccharides (LPSs) has been found to offer protection against allergic asthma, infants residing in urban environments are increasingly exposed to environmental pollutants. Utilizing limulus lysate test screens and virtual screening models, we identified pollutants that can modulate LPS bioactivity. This investigation revealed that bisphenol A (BPA), a chemical commonly used in numerous household items and previously implicated in obesity and cancer, effectively neutralizes LPS. In-depth mechanistic analyses showed that BPA specifically binds to the lipid A component of LPS, leading to inactivation. This interaction eliminates the immunostimulatory activity of LPS, making mice more susceptible to house dust mite (HDM)-induced allergic asthma. BPA reactivates lung epithelial cells, consequently amplifying type 2 responses to HDMs in dendritic cells. This chemical interplay provides new insights into the pathophysiology of asthma in relation to human exposure. Understanding the intricate relationships between environmental chemicals and microbial antigens, as well as their impacts on innate immunity, is critical for the development of intervention strategies to address immune disorders resulting from urbanization. |
| first_indexed | 2024-10-01T03:18:37Z |
| format | Journal Article |
| id | ntu-10356/173165 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:18:37Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1731652024-01-19T15:33:34Z A missing jigsaw within the hygiene hypothesis: low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection Wang, Mengjing Qu, Jing Yang, Junjie Zhang, Tian Tan, Wei Ren Liao, Shumin Chen, Xing Liu, Yingzi Long, Xiang Li, Xue Xia, Yun Tan, Nguan Soon Li, Liang Fang, Mingliang School of Civil and Environmental Engineering Lee Kong Chian School of Medicine (LKCMedicine) Engineering::Environmental engineering Science::Medicine Allergic Asthma Environmental Pollutants The rising occurrence of allergic asthma in early life across industrialized countries suggests that environmental factors play a crucial role in determining asthma susceptibility and severity. While prior exposure to microbial lipopolysaccharides (LPSs) has been found to offer protection against allergic asthma, infants residing in urban environments are increasingly exposed to environmental pollutants. Utilizing limulus lysate test screens and virtual screening models, we identified pollutants that can modulate LPS bioactivity. This investigation revealed that bisphenol A (BPA), a chemical commonly used in numerous household items and previously implicated in obesity and cancer, effectively neutralizes LPS. In-depth mechanistic analyses showed that BPA specifically binds to the lipid A component of LPS, leading to inactivation. This interaction eliminates the immunostimulatory activity of LPS, making mice more susceptible to house dust mite (HDM)-induced allergic asthma. BPA reactivates lung epithelial cells, consequently amplifying type 2 responses to HDMs in dendritic cells. This chemical interplay provides new insights into the pathophysiology of asthma in relation to human exposure. Understanding the intricate relationships between environmental chemicals and microbial antigens, as well as their impacts on innate immunity, is critical for the development of intervention strategies to address immune disorders resulting from urbanization. Published version This work was primarily supported by National Natural Science Foundation of China (22376032, 81900071), National Key Research and Development Program of China (2022YFC3702601, 2022YFC2304400, 2022YFC2304401), and the Natural Science Foundation of Guangdong Province of China (2021A1515010004). Dr. Mingliang Fang was further supported by Agilent University Relations: ACT-UR Program and Grant ID #4863, and the “Xiaomi” young investigator award. 2024-01-16T01:50:27Z 2024-01-16T01:50:27Z 2023 Journal Article Wang, M., Qu, J., Yang, J., Zhang, T., Tan, W. R., Liao, S., Chen, X., Liu, Y., Long, X., Li, X., Xia, Y., Tan, N. S., Li, L. & Fang, M. (2023). A missing jigsaw within the hygiene hypothesis: low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection. PNAS Nexus, 2(11), 1-10. https://dx.doi.org/10.1093/pnasnexus/pgad312 2752-6542 https://hdl.handle.net/10356/173165 10.1093/pnasnexus/pgad312 37954159 2-s2.0-85177841913 11 2 1 10 en PNAS Nexus © The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. application/pdf |
| spellingShingle | Engineering::Environmental engineering Science::Medicine Allergic Asthma Environmental Pollutants Wang, Mengjing Qu, Jing Yang, Junjie Zhang, Tian Tan, Wei Ren Liao, Shumin Chen, Xing Liu, Yingzi Long, Xiang Li, Xue Xia, Yun Tan, Nguan Soon Li, Liang Fang, Mingliang A missing jigsaw within the hygiene hypothesis: low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection |
| title | A missing jigsaw within the hygiene hypothesis: low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection |
| title_full | A missing jigsaw within the hygiene hypothesis: low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection |
| title_fullStr | A missing jigsaw within the hygiene hypothesis: low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection |
| title_full_unstemmed | A missing jigsaw within the hygiene hypothesis: low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection |
| title_short | A missing jigsaw within the hygiene hypothesis: low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection |
| title_sort | missing jigsaw within the hygiene hypothesis low dose bisphenol a exposure attenuates lipopolysaccharide induced asthma protection |
| topic | Engineering::Environmental engineering Science::Medicine Allergic Asthma Environmental Pollutants |
| url | https://hdl.handle.net/10356/173165 |
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