Mallek Nicholas M, Martin Elizabeth M, Dailey Lisa A, McCullough Shaun D
Curriculum in Toxicology and Environmental Medicine, University of North Carolina, Chapel Hill, NC, United States.
Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Durham, NC, United States.
Front Toxicol. 2024 Jan 23;5:1264331. doi: 10.3389/ftox.2023.1264331. eCollection 2023.
Differentiated primary human bronchial epithelial cell (dpHBEC) cultures grown under air-liquid interface (ALI) conditions exhibit key features of the human respiratory tract and are thus critical for respiratory research as well as efficacy and toxicity testing of inhaled substances (, consumer products, industrial chemicals, and pharmaceuticals). Many inhalable substances (, particles, aerosols, hydrophobic substances, reactive substances) have physiochemical properties that challenge their evaluation under ALI conditions . Evaluation of the effects of these methodologically challenging chemicals (MCCs) is typically conducted by "liquid application," involving the direct application of a solution containing the test substance to the apical, air-exposed surface of dpHBEC-ALI cultures. We report that the application of liquid to the apical surface of a dpHBEC-ALI co-culture model results in significant reprogramming of the dpHBEC transcriptome and biological pathway activity, alternative regulation of cellular signaling pathways, increased secretion of pro-inflammatory cytokines and growth factors, and decreased epithelial barrier integrity. Given the prevalence of liquid application in the delivery of test substances to ALI systems, understanding its effects provides critical infrastructure for the use of systems in respiratory research as well as in the safety and efficacy testing of inhalable substances.
在气液界面（ALI）条件下培养的分化原代人支气管上皮细胞（dpHBEC）培养物展现出人类呼吸道的关键特征，因此对于呼吸研究以及吸入物质（消费品、工业化学品和药物）的功效和毒性测试至关重要。许多可吸入物质（颗粒、气溶胶、疏水物质、活性物质）具有的物理化学性质对在ALI条件下对其进行评估构成挑战。对这些方法上具有挑战性的化学物质（MCC）的影响评估通常通过“液体应用”进行，即将含有测试物质的溶液直接应用于dpHBEC-ALI培养物的顶端、暴露于空气的表面。我们报告称，将液体应用于dpHBEC-ALI共培养模型的顶端表面会导致dpHBEC转录组和生物途径活性的显著重编程、细胞信号通路的交替调节、促炎细胞因子和生长因子分泌增加以及上皮屏障完整性降低。鉴于在将测试物质递送至ALI系统中液体应用的普遍性，了解其影响为在呼吸研究以及可吸入物质的安全性和功效测试中使用该系统提供了关键的基础条件。
