AUTHOR=Ji Jie , Jansen Katja , Kessler Vadim , Seisenbaeva Gulaim , Gerde Per , Malmlöf Maria , Palmberg Lena , Upadhyay Swapna 

TITLE=Cell line-based in vitro models of normal and chronic bronchitis-like airway mucosa to study the toxic potential of aerosolized palladium nanoparticles

JOURNAL=Frontiers in Medicine

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1422792

DOI=10.3389/fmed.2024.1422792

ISSN=2296-858X

ABSTRACT=<sec id="sec1"><title>Background</title><p>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 <italic>in vitro</italic> airway models to assess the toxic potential of Pd-NP in normal (Non-CB) and chronic bronchitis-like (CB-like) mucosa models.</p></sec><sec id="sec2"><title>Methods</title><p>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<sup>2</sup>) using XposeALI<sup>®</sup> and clean air as a control. After 24 h of incubation, the expression of inflammatory (<italic>IL6</italic>, <italic>CXCL8</italic>, <italic>TNFα</italic>, and <italic>NFKB</italic>), oxidative stress (<italic>HMOX1</italic>, <italic>SOD3</italic>, <italic>GPx</italic>, and <italic>GSTA1</italic>), and tissue injury/repair (<italic>MMP9/TIMP1</italic>) 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.</p></sec><sec id="sec3"><title>Results</title><p>Significantly (<italic>p</italic> &lt; 0.05) increased expressions of <italic>CXCL8</italic>, <italic>IL6</italic>, and <italic>NFKB</italic> were observed at the highest dose of Pd-NP in CB-like models. However, in Non-CB mucosa models, a maximum effect on <italic>TNFα</italic> and <italic>NFKB</italic> expression was observed at a medium Pd-NP dose. In Non-CB mucosa models, <italic>SOD3</italic> showed a clear dose-dependent response to Pd-NP exposure, while <italic>GSTA1</italic> expression was significantly increased (<italic>p</italic> &lt; 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.</p></sec><sec id="sec4"><title>Conclusion</title><p>The combination of our Non-CB and CB-like mucosa models with the XposeALI<sup>®</sup> system for aerosolized nanoparticle exposure closely mimics <italic>in vivo</italic> lung environments and cell-particle interactions. Results from these models, utilizing accessible cell lines, will maximize the reliability of <italic>in vitro</italic> findings in human health risk assessment.</p></sec>