Ming Wang1, Ge Tan2, Andrzej Eljaszewicz3, Yifan Meng1, Paulina Wawrzyniak4, Swati Acharya5, Can Altunbulakli4, Patrick Westermann4, Anita Dreher4, Liying Yan6, Chengshuo Wang7, Mubeccel Akdis4, Luo Zhang7, Kari C Nadeau5, Cezmi A Akdis8. 1. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and the Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, and the Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China. 2. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and the Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Functional Genomics Center Zurich, ETH Zurich/University of Zurich, Zurich, Switzerland. 3. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and the Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland. 4. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and the Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland. 5. Sean N Parker Center for Allergy and Asthma Research at Stanford University, Department of Medicine, Stanford University School of Medicine, Stanford, Calif. 6. EpigenDx, Hopkinton, Mass. 7. Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, and the Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China. 8. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and the Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland. Electronic address: akdisac@siaf.uzh.ch.
Abstract
BACKGROUND: Defects in the epithelial barrier have recently been associated with asthma and other allergies. The influence of laundry detergents on human bronchial epithelial cells (HBECs) and their barrier function remain unknown. OBJECTIVE: We investigated the effects of laundry detergents on cytotoxicity, barrier function, the transcriptome, and the epigenome in HBECs. METHODS: Air-liquid interface cultures of primary HBECs from healthy control subjects, patients with asthma, and patients with chronic obstructive pulmonary disease were exposed to laundry detergents and detergent residue after rinsing. Cytotoxicity and epithelial barrier function were evaluated. RNA sequencing, Assay for Transposase Accessible Chromatin with high-throughput sequencing, and DNA methylation arrays were used for checking the transcriptome and epigenome. RESULTS: Laundry detergents and rinse residue showed dose-dependent toxic effects on HBECs, with irregular cell shape and leakage of lactate dehydrogenase after 24 hours of exposure. A disrupted epithelial barrier function was found with decreased transepithelial electrical resistance, increased paracellular flux, and stratified tight junction (TJ) immunostaining in HBECs exposed to laundry detergent at 1:25,000 dilutions or rinse residue at further 1:10 dilutions. RNA sequencing analysis showed that lipid metabolism, apoptosis progress, and epithelially derived alarmin-related gene expression were upregulated, whereas cell adhesion-related gene expression was downregulated by laundry detergent at 1:50,000 dilutions after 24 hours of exposure without substantially affecting chromatin accessibility and DNA methylation. CONCLUSION: Our data demonstrate that laundry detergents, even at a very high dilution, and rinse residue show significant cell-toxic and directly disruptive effects on the TJ barrier integrity of HBECs without affecting the epigenome and TJ gene expression.
BACKGROUND: Defects in the epithelial barrier have recently been associated with asthma and other allergies. The influence of laundry detergents on human bronchial epithelial cells (HBECs) and their barrier function remain unknown. OBJECTIVE: We investigated the effects of laundry detergents on cytotoxicity, barrier function, the transcriptome, and the epigenome in HBECs. METHODS: Air-liquid interface cultures of primary HBECs from healthy control subjects, patients with asthma, and patients with chronic obstructive pulmonary disease were exposed to laundry detergents and detergent residue after rinsing. Cytotoxicity and epithelial barrier function were evaluated. RNA sequencing, Assay for Transposase Accessible Chromatin with high-throughput sequencing, and DNA methylation arrays were used for checking the transcriptome and epigenome. RESULTS: Laundry detergents and rinse residue showed dose-dependent toxic effects on HBECs, with irregular cell shape and leakage of lactate dehydrogenase after 24 hours of exposure. A disrupted epithelial barrier function was found with decreased transepithelial electrical resistance, increased paracellular flux, and stratified tight junction (TJ) immunostaining in HBECs exposed to laundry detergent at 1:25,000 dilutions or rinse residue at further 1:10 dilutions. RNA sequencing analysis showed that lipid metabolism, apoptosis progress, and epithelially derived alarmin-related gene expression were upregulated, whereas cell adhesion-related gene expression was downregulated by laundry detergent at 1:50,000 dilutions after 24 hours of exposure without substantially affecting chromatin accessibility and DNA methylation. CONCLUSION: Our data demonstrate that laundry detergents, even at a very high dilution, and rinse residue show significant cell-toxic and directly disruptive effects on the TJ barrier integrity of HBECs without affecting the epigenome and TJ gene expression.
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