Organotypic culture of human primary bronchial epithelial cells is a useful in vitro system to study normal biological processes and
lung disease mechanisms, to develop new
therapies, and to assess the
biological perturbations induced by
environmental pollutants. Herein, we investigate whether the perturbations induced by cigarette
smoke (CS) and observed in the epithelium of smokers' airways are reproducible in this in vitro system (AIR-100 tissue), which has been shown to recapitulate most of the characteristics of the human bronchial epithelium. Human AIR-100 tissues were exposed to mainstream CS for 7, 14, 21, or 28 min at the air-liquid interface, and we investigated various
biological endpoints [e.g., gene expression and
microRNA profiles,
matrix metalloproteinase 1 (MMP-1) release] at multiple postexposure time points (0.5, 2, 4, 24, 48 h). By performing a Gene Set Enrichment Analysis, we observed a significant enrichment of human smokers' bronchial epithelium gene signatures derived from different public transcriptomics datasets in CS-exposed AIR-100 tissue. Comparison of in vitro
microRNA profiles with
microRNA data from healthy smokers highlighted various highly translatable
microRNAs associated with
inflammation or with cell cycle processes that are known to be perturbed by CS in lung tissue. We also found a dose-dependent increase of MMP-1 release by AIR-100 tissue 48 h after CS exposure in agreement with the known effect of CS on this
collagenase expression in smokers' tissues. In conclusion, a similar
biological perturbation than the one observed in vivo in smokers' airway epithelium could be induced after a single CS exposure of a human organotypic bronchial epithelium-like tissue culture.