Cells grown in monocultures are widely used to model lung tissue. As a result of these culture conditions, these cells exhibit poor morphological similarity to those present in in vivo lung tissue. MucilAir™, a 3-D in vitro model comprising human basal, goblet and ciliated cells, represents a fully differentiated respiratory epithelium that can be used as an alternative and a more realistic system. The aim of our study was to compare the effects of short-term and long-term exposure to two polycyclic aromatic hydrocarbons (PAHs) — benzo[a]pyrene (B[a]P) and 3-nitrobenzanthrone (3-NBA) — using MucilAir as a model of human lung tissue. Two concentrations (0.1 μM and 1 μM) were tested at three time points (24 hours, 7 days and 28 days). Several aspects were assessed: cytotoxicity (lactate dehydrogenase (LDH) release), integrity of the cell layer (transepithelial electrical resistance (TEER)), induction of oxidative stress (reactive oxygen species production) and changes in the expression of selected genes involved in PAH metabolism (CYP1A1 and AKR1C2) and the antioxidant response (ALDH3A1, SOD1, SOD2, GPX1, CAT, HMOX1 and TXNRD1). The results showed that exposure to B[a]P caused a spike in LDH release at day 5. Exposure to 3-NBA caused a number of spikes in LDH release, starting at day 5, and a decrease in TEER after 11 days. CYP1A1 gene expression was upregulated after the 7-day and 28-day B[a]P exposures, as well as after the 24-hour and 7-day 3-NBA exposures. HMOX1 and SOD1 were downregulated after both 24-hour PAH treatments. HMOX1 was upregulated after a 1-week exposure to 3-NBA. There were no significant changes in the messenger RNA (mRNA) levels of AKR1C2, ALDH3A1, TXNRD1, SOD2, GPX1 or CAT. These results illustrate the potential use of this 3-D in vitro lung tissue model in studying the effects of chronic exposure to PAHs.

中文翻译：

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MucilAir™ 模型对多环芳烃的短期和长期暴露

在单一培养中生长的细胞被广泛用于模拟肺组织。由于这些培养条件，这些细胞与体内肺组织中存在的细胞表现出较差的形态相似性。MucilAir™ 是一种包含人类基底细胞、杯状细胞和纤毛细胞的 3-D 体外模型，代表了一种完全分化的呼吸上皮，可用作替代和更现实的系统。我们研究的目的是比较短期和长期暴露于两种多环芳烃 (PAH) — 苯并 [a] 芘 (B[a]P) 和 3-硝基苯并蒽酮 (3-NBA) — 的影响。使用 MucilAir 作为人类肺组织模型。在三个时间点（24 小时、7 天和 28 天）测试了两种浓度（0.1 μM 和 1 μM）。评估了几个方面：细胞毒性（乳酸脱氢酶（LDH）释放），细胞层的完整性（跨上皮电阻 (TEER)）、氧化应激的诱导（活性氧的产生）以及参与 PAH 代谢（CYP1A1 和 AKR1C2）和抗氧化反应（ALDH3A1、SOD1、 SOD2、GPX1、CAT、HMOX1 和 TXNRD1)。结果表明，暴露于 B[a]P 导致第 5 天 LDH 释放量激增。暴露于 3-NBA 导致 LDH 释放量激增，从第 5 天开始，并在 11 天后降低 TEER。CYP1A1 基因表达在 7 天和 28 天 B[a]P 暴露后以及在 24 小时和 7 天 3-NBA 暴露后上调。HMOX1 和 SOD1 在 24 小时 PAH 处理后均下调。HMOX1 在接触 3-NBA 1 周后上调。AKR1C2、ALDH3A1、TXNRD1、SOD2、GPX1 或 CAT 的信使 RNA (mRNA) 水平没有显着变化。这些结果说明了这种 3-D 体外肺组织模型在研究长期暴露于多环芳烃的影响中的潜在用途。