Abstract
BackgroundExposure to agents via inhalation is of great concerns both in workplace environment and in the daily contact with particles in the ambient air. Reliable human airway exposure systems will most likely replace animal experiment in future toxicity assessment studies of inhaled agents.MethodsIn this study, we successfully established a combination of an exposure system (XposeALI) with 3D models mimicking both healthy and chronic bronchitis-like mucosa by co-culturing human primary bronchial epithelial cells (PBEC) and fibroblast at air-liquid interface (ALI). Light-, confocal microscopy, scanning- and transmission electron microscopy, transepithelial electrical resistance (TEER) measurement and RT-PCR were performed to identify how the PBEC differentiated under ALI culture condition. Both models were exposed to palladium (Pd) nanoparticles which sized 6–10 nm, analogous to those released from modern car catalysts, at three different concentrations utilizing the XposeALI module of the PreciseInhale® exposure system.ResultsExposing the 3D models to Pd nanoparticles induced increased secretion of IL-8, yet the chronic bronchitis-like model released significantly more IL-8 than the normal model. The levels of IL-8 in basal medium (BM) and apical lavage medium (AM) were in the same ranges, but the secretion of MMP-9 was significantly higher in the AM compared to the BM.ConclusionThis combination of relevant human bronchial mucosa models and sophisticated exposure system can mimic in vivo conditions and serve as a useful alternative animal testing tool when studying adverse effects in humans exposed to aerosols, air pollutants or particles in an occupational setting.
Highlights
As more and more ethical concerns are raised over the use of animal models in medical research, attempts are made to reduce and replace animal experiments
The levels of IL-8 in basal medium (BM) and apical lavage medium (AM) were in the same ranges, but the secretion of matrix metallopeptidase 9 (MMP-9) was significantly higher in the AM compared to the BM
To identify the appearance of primary bronchial epithelial cells (PBEC) grown under air-liquid interface (ALI) culture conditions, hematoxylin and eosin (H&E) analysis of model cross sections was carried out of 3D model after culturing at ALI for 2 weeks (Fig 1A)
Summary
As more and more ethical concerns are raised over the use of animal models in medical research, attempts are made to reduce and replace animal experiments. Treatment of epithelial cells with Interleukin-13 (IL-13) induced mucus-producing cells, metaplasia or hyperplasia as well as increased expression and production of MUC5AC[10] These features are major characteristics of chronic bronchitis. XposeALI is an in vitro cell exposure system where cells cultivated under ALI conditions can be exposed to aerosol of interest by being coupled to the PreciseInhale aerosol generator which generates aerosols from a variety of dry powders through de-agglomeration [11]. This set-up allows aerosol exposures of cell cultures to respirable particles. Reliable human airway exposure systems will most likely replace animal experiment in future toxicity assessment studies of inhaled agents
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