Ji Jie, Jansen Katja, Kessler Vadim, Seisenbaeva Gulaim, Gerde Per, Malmlöf Maria, Palmberg Lena, Upadhyay Swapna
Unit of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Inorganic Bionanotechnology Unit, Department of Chemistry and Biotechnology, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
Front Med (Lausanne). 2024 Oct 8;11:1422792. doi: 10.3389/fmed.2024.1422792. eCollection 2024.
Physiologically relevant cell line-based models of human airway mucosa are needed to assess nanoparticle-mediated pulmonary toxicity for any xenbiotics expsoure study. Palladium nanoparticles (Pd-NP) originating from catalytic converters in vehicles pose health risks. We aimed to develop airway models to assess the toxic potential of Pd-NP in normal (Non-CB) and chronic bronchitis-like (CB-like) mucosa models.
Bronchial mucosa models were developed using Epithelial cells (16HBE: apical side) co-cultured with fibroblast (basal side) at an air-liquid interface. Furthermore, both Non-CB and CB-like (IL-13 treatment) models with increased numbers of goblet cells were used. The models were exposed to 3 different doses of aerosolized Pd-NP (0.2, 0.3, and 6 μg/cm) using XposeALI and clean air as a control. After 24 h of incubation, the expression of inflammatory (, , , and ), oxidative stress (, , , and ), and tissue injury/repair () markers was assessed using qRT-PCR. The secretion of CXCL-8 and the expression of a tissue injury/repair marker (MMP-9) were measured via ELISA.
Significantly ( < 0.05) increased expressions of , , and were observed at the highest dose of Pd-NP in CB-like models. However, in Non-CB mucosa models, a maximum effect on and expression was observed at a medium Pd-NP dose. In Non-CB mucosa models, showed a clear dose-dependent response to Pd-NP exposure, while expression was significantly increased ( < 0.05) only at the lowest dose of Pd-NP. The secretion of CXCL-8 increased in a dose-dependent manner in the Non-CB mucosa models following exposure to Pd-NP. In CB-like models, exposure to high concentrations of Pd-NP significantly increased the release of MMP-9 compared to that in other exposure groups.
The combination of our Non-CB and CB-like mucosa models with the XposeALI system for aerosolized nanoparticle exposure closely mimics lung environments and cell-particle interactions. Results from these models, utilizing accessible cell lines, will maximize the reliability of findings in human health risk assessment.
对于任何外源性物质暴露研究，需要基于生理相关细胞系的人气道黏膜模型来评估纳米颗粒介导的肺毒性。车辆催化转化器产生的钯纳米颗粒（Pd-NP）会带来健康风险。我们旨在开发气道模型，以评估Pd-NP在正常（非慢性支气管炎样，Non-CB）和慢性支气管炎样（CB样）黏膜模型中的潜在毒性。
使用上皮细胞（16HBE：顶侧）与成纤维细胞（基底侧）在气液界面共培养建立支气管黏膜模型。此外，还使用了杯状细胞数量增加的非慢性支气管炎样和CB样（白细胞介素-13处理）模型。使用XposeALI将模型暴露于3种不同剂量的雾化Pd-NP（0.2、0.3和6μg/cm），并以清洁空气作为对照。孵育24小时后，使用qRT-PCR评估炎症（白细胞介素-6、白细胞介素-8、肿瘤坏死因子-α和白细胞介素-1β）、氧化应激（超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶和丙二醛）和组织损伤/修复（基质金属蛋白酶-9）标志物的表达。通过酶联免疫吸附测定法测量CXCL-8的分泌和组织损伤/修复标志物（基质金属蛋白酶-9）的表达。
在CB样模型中，在最高剂量的Pd-NP下观察到白细胞介素-6、白细胞介素-8和肿瘤坏死因子-α的表达显著（P<0.05）增加。然而，在非慢性支气管炎样黏膜模型中，在中等剂量的Pd-NP下观察到对白细胞介素-1β和基质金属蛋白酶-9表达的最大影响。在非慢性支气管炎样黏膜模型中，超氧化物歧化酶对Pd-NP暴露表现出明显的剂量依赖性反应，而丙二醛表达仅在最低剂量的Pd-NP下显著增加（P<0.05）。在非慢性支气管炎样黏膜模型中，暴露于Pd-NP后，CXCL-8的分泌呈剂量依赖性增加。在CB样模型中，与其他暴露组相比，暴露于高浓度的Pd-NP显著增加了基质金属蛋白酶-9的释放。
我们的非慢性支气管炎样和CB样黏膜模型与用于雾化纳米颗粒暴露的XposeALI系统相结合，紧密模拟了肺部环境和细胞-颗粒相互作用。利用可获取的细胞系，这些模型的结果将最大限度地提高人类健康风险评估中研究结果的可靠性。
