RT Journal Article
SR Electronic
T1 Diesel exhaust particles and TNF-alpha or LPS induce pro-inflammatory pathways, including TSLP expression, in bronchial epithelial cells
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 211
DO 10.1183/23120541.LSC-2022.211
VO 8
IS suppl 8
A1 Fien Gysens
A1 Annelies Bontinck
A1 Aurélie Crabbé
A1 Eric De Bony De Lavergne
A1 Ken Bracke
A1 Guy Brusselle
A1 Tania Maes
A1 Pieter Mestdagh
YR 2022
UL http://openres.ersjournals.com/content/8/suppl_8/211.abstract
AB 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.FootnotesCite this article as ERJ Open Research 2022; 8: Suppl. 8, 211.This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).