{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T16:28:29Z","timestamp":1788020909565,"version":"build-2784847793"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats: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 <jats:italic>in vitro<\/jats:italic> airway models to assess the toxic potential of Pd-NP in normal (Non-CB) and chronic bronchitis-like (CB-like) mucosa models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats: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\u2009\u03bcg\/cm<jats:sup>2<\/jats:sup>) using XposeALI<jats:sup>\u00ae<\/jats:sup> and clean air as a control. After 24\u2009h of incubation, the expression of inflammatory (<jats:italic>IL6<\/jats:italic>, <jats:italic>CXCL8<\/jats:italic>, <jats:italic>TNF\u03b1<\/jats:italic>, and <jats:italic>NFKB<\/jats:italic>), oxidative stress (<jats:italic>HMOX1<\/jats:italic>, <jats:italic>SOD3<\/jats:italic>, <jats:italic>GPx<\/jats:italic>, and <jats:italic>GSTA1<\/jats:italic>), and tissue injury\/repair (<jats:italic>MMP9\/TIMP1<\/jats:italic>) markers was assessed using qRT\u2013PCR. The secretion of CXCL-8 and the expression of a tissue injury\/repair marker (MMP-9) were measured via ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significantly (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05) increased expressions of <jats:italic>CXCL8<\/jats:italic>, <jats:italic>IL6<\/jats:italic>, and <jats:italic>NFKB<\/jats:italic> were observed at the highest dose of Pd-NP in CB-like models. However, in Non-CB mucosa models, a maximum effect on <jats:italic>TNF\u03b1<\/jats:italic> and <jats:italic>NFKB<\/jats:italic> expression was observed at a medium Pd-NP dose. In Non-CB mucosa models, <jats:italic>SOD3<\/jats:italic> showed a clear dose-dependent response to Pd-NP exposure, while <jats:italic>GSTA1<\/jats:italic> expression was significantly increased (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05) 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The combination of our Non-CB and CB-like mucosa models with the XposeALI<jats:sup>\u00ae<\/jats:sup> system for aerosolized nanoparticle exposure closely mimics <jats:italic>in vivo<\/jats:italic> lung environments and cell-particle interactions. Results from these models, utilizing accessible cell lines, will maximize the reliability of <jats:italic>in vitro<\/jats:italic> findings in human health risk assessment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2024.1422792","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T04:40:58Z","timestamp":1728362458000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Cell line-based in vitro models of normal and chronic bronchitis-like airway mucosa to study the toxic potential of aerosolized palladium nanoparticles"],"prefix":"10.3389","volume":"11","author":[{"given":"Jie","family":"Ji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim","family":"Kessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulaim","family":"Seisenbaeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Gerde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Malml\u00f6f","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Palmberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swapna","family":"Upadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"4345","DOI":"10.3390\/ijms24054345","article-title":"Outdoor 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