洗衣剂和漂洗后的洗涤剂残留物会直接破坏人支气管上皮细胞的紧密连接屏障完整性。

Laundry detergents and detergent residue after rinsing directly disrupt tight junction barrier integrity in human bronchial epithelial cells.

机构信息

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.

出版信息

J Allergy Clin Immunol. 2019 May;143(5):1892-1903. doi: 10.1016/j.jaci.2018.11.016. Epub 2018 Nov 27.

DOI:10.1016/j.jaci.2018.11.016

PMID:30500342

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.

摘要

背景

最近，上皮屏障缺陷与哮喘和其他过敏有关。洗衣剂对人支气管上皮细胞 (HBEC) 及其屏障功能的影响尚不清楚。

目的

我们研究了洗衣剂对 HBEC 细胞毒性、屏障功能、转录组和表观基因组的影响。

方法

用来自健康对照者、哮喘患者和慢性阻塞性肺疾病患者的原代 HBEC 进行气液界面培养，然后用洗衣剂和漂洗后的洗涤剂残留进行暴露。评估细胞毒性和上皮屏障功能。使用 RNA 测序、高通量测序的转座酶可及染色质测定法和 DNA 甲基化阵列检查转录组和表观基因组。

结果

洗衣剂和漂洗残留对 HBEC 具有剂量依赖性的毒性作用，暴露 24 小时后细胞形状不规则，乳酸脱氢酶漏出。在 1:25000 稀释的洗衣剂或进一步稀释 1:10 的漂洗残留作用下，HBEC 的上皮屏障功能受损，表现为跨上皮电阻降低、旁通透性增加和紧密连接 (TJ) 免疫染色分层。RNA 测序分析显示，暴露于 1:50000 稀释的洗衣剂 24 小时后，脂质代谢、凋亡进程和上皮衍生警报素相关基因表达上调，而细胞黏附相关基因表达下调，但对染色质可及性和 DNA 甲基化没有显著影响。