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CORESTA Congress, Paris, 2006, SS 30

Human bronchial epithelial cell transcriptome: gene expression changes following acute exposure to whole cigarette smoke in vitro

PATWARDHAN S.; MAUNDERS H.; PHILLIPS J.; CLACK A.; RICHTER A.
Advanced Technologies Ltd., Cambridge, UK

Cigarette smoke is a complex mixture of over 4000 constituents. Its effects on cell biology are poorly understood, partly because whole smoke exposure in vitro is technically challenging. To investigate the effects of smoke on cell signalling and function, in this study a 3-D air-liquid interface model of tracheobronchial epithelium, grown from primary human lung epithelial cells, was exposed to air or one of two sub-toxic doses of whole mainstream cigarette smoke for 1 h in a purpose-designed chamber. Gene expression profiles were then determined at 1, 6 and 24 h post exposure using Affymetrix microarrays. Cells from three different donors were used in the study and the experiment was performed on three separate occasions for each donor. Genes significantly and consistently up or down-regulated by smoke, compared to the air control, in all experiments were determined. An effect of the low dose of smoke was observed at 6 h but gene expression profiles were similar to the air control at 24 h. By comparison, the high dose of smoke induced irreversible changes in expression. The gene lists for this dose were assigned to functional categories and mapped to signalling pathways. Effects were observed on many cellular processes including xenobiotic metabolism, oxidant/antioxidant balance and DNA damage and repair. Notably, there was very marked down-regulation of the transforming growth factor-beta pathway that has not been previously reported. This study provides important data on the acute effects of whole cigarette smoke on mucociliary epithelium and may be used to gain a greater understanding of smoke toxicity.