Diesel exhaust particles and TNF-alpha or LPS induce pro-inflammatory pathways, including TSLP expression, in bronchial epithelial cells

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Asthma is a complex inflammatory disease involving many cell types. Environmental exposures are important in asthma development and severity. We aimed to set up a bronchial epithelial cell model with exposures to noxious environmental factors to model the biological pathways that are dysregulated in airway epithelium of asthma patients. Therefore, submerged 2D cultures of BEAS-2B cells (normal human bronchial epithelial cells) were exposed to various concentrations of diesel exhaust particles (DEP) and/or TNF-alpha or lipopolysaccharide (LPS) derived from Pseudomonas aeruginosa for 24 hours, followed by evaluation of pathway activities by RNA-sequencing and gene-set enrichment analysis. Compared to an untreated control, increasing concentrations of DEP had limited impact on inflammatory pathways while the pro-inflammatory cytokine TNF-alpha or LPS strongly induced immune pathways and IL-8 expression. Notably, combining DEP with TNF-alpha or LPS resulted in a DEP dose dependent induction of thymic stromal lymphopoietin (TSLP), a crucial epithelial alarmin that drives allergic and eosinophilic inflammation and serves as a therapeutic target in asthma patients. There are also more significantly dysregulated pathways when agents were combined. We are currently establishing 3D BEAS-2B cell cultures for DEP-LPS-TNF-alpha exposure to further improve model relevance. In conclusion, combining DEP with LPS or TNF-alpha induces biologically relevant gene expression changes in BEAS-2B cells, providing an interesting model to study various inflammatory pathways in asthma.

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