Human bronchial epithelial cells exposed in vitro to cigarette smoke at the air-liquid interface resemble bronchial epithelium from human smokers.

Abstract

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.

• Authors: Carole Mathis, Carine Poussin, Dirk Weisensee, Stephan Gebel, Arnd Hengstermann, Alain Sewer, Vincenzo Belcastro, Yang Xiang, Sam Ansari, Sandra Wagner, Julia Hoeng, Manuel C Peitsch
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 304 Issue 7 Pg. L489-503 (Apr 01 2013) ISSN: 1522-1504 [Electronic] United States
• PMID: 23355383 (Publication Type: Journal Article)

Chemical References

• MicroRNAs
• Tobacco Smoke Pollution
• MMP1 protein, human
• Matrix Metalloproteinase 1

Topics

• Adult
• Bronchi (enzymology, pathology)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Epithelial Cells (enzymology, pathology)
• Gene Expression Regulation, Enzymologic (drug effects)
• Humans
• Inflammation (chemically induced, enzymology, pathology)
• Male
• Matrix Metalloproteinase 1 (biosynthesis)
• MicroRNAs (metabolism)
• Smoking (metabolism, pathology)
• Time Factors
• Tobacco Smoke Pollution (adverse effects)