A missing jigsaw within the hygiene hypothesis: Low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection

Mengjing Wang1,2; Jing Qu3; Junjie Yang2; Tian Zhang4; Wei Ren Tan4; Shumin Liao5; Xing,Chen6; Yingzi,Liu7; Xiang,Long8; Xue,Li6; Yun,Xia4; Nguan Soon,Tan4; Liang,Li5,9,10; Mingliang,Fang1

2023-11-07

10.1093/pnasnexus/pgad312

PNAS Nexus   影响因子和分区

2752-6542

2752-6542

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.

allergic asthma environmental pollutants lipopolysaccharides (LPSs) bisphenol A (BPA) house dust mite (HDM) asthma pathophysiology

[来源记录]

SCI ; ESCI

英语

通讯

National Natural Science Foundation of China["22376032","81900071"] ; National Key Research and Development Program of China["2022YFC3702601","2022YFC2304400","2022YFC2304401"] ; Natural Science Foundation of Guangdong Province of China[2021A1515010004] ; Agilent University Relations: ACT-UR Program[4863]

Science & Technology - Other Topics ; Social Sciences - Other Topics

Multidisciplinary Sciences ; Social Sciences, Interdisciplinary

WOS:001156104200003

Oxford University Press (OUP)

人工提交

1.Department of Environmental Science and Engineering, Fudan University, Shanghai 200433, China.
2.School of Civil and Environmental Engineering, Nanyang Technological University, Singapore 639798, Singapore.
3.Department of Pathogen Biology, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
4.Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore.
5.Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China
6.Institute of Mass Spectrometer and Atmospheric Environment, Jinan University, Guangzhou 510632, China.
7.Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen 518036, China.
8.Department of Respiratory Medicine and Critical Care, Peking University Shenzhen Hospital, Shenzhen 518036, China.
9.Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
10.Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, Shenzhen 518055, China.

Mengjing Wang,Jing Qu,Junjie Yang,et al. A missing jigsaw within the hygiene hypothesis: Low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection[J]. PNAS Nexus,2023,2(11):1-10.

Mengjing Wang.,Jing Qu.,Junjie Yang.,Tian Zhang.,Wei Ren Tan.,...&Mingliang,Fang.(2023).A missing jigsaw within the hygiene hypothesis: Low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection.PNAS Nexus,2(11),1-10.

Mengjing Wang,et al."A missing jigsaw within the hygiene hypothesis: Low-dose bisphenol A exposure attenuates lipopolysaccharide-induced asthma protection".PNAS Nexus 2.11(2023):1-10.