IN VITRO EXPOSURE OF ORGANOTYPICAL 3D EPITHELIAL TISSUES TO CIGARETTE SMOKE AS A POTENTIAL ALTERNATIVE TO RODENT INHALATION STUDIES.

Airway epithelium is the initial barrier affected by toxic gases or particles in the atmosphere, such as cigarette smoke (CS), which induces, among other things, inflammatory processes that can lead to COPD and tissue remodeling (Takizawa 2001, Yoshida 2007). Here we describe an in vitro test system that examines the toxicological effects of single or repeated CS exposure on human organotypically reconstituted 3D epithelial tissues (EpiAirway™, MatTek). Tissues were exposed at the air liquid interface to either fresh air or to mainstream smoke from the Reference Cigarette 3R4F in the VITROCELL® system (3-well or 24-well exposure chamber). The objective of the study was to demonstrate whether exposure of human lung tissue to whole smoke in vitro can induce similar effects as observed in rodent inhalation studies with regard to selected gene and protein expression.

Alcian blue –periodic acid schiff, CYP1A1, Cytochrome P450 1A1 (CYP1A1), EpiAirway (AIR-100-PC12), Heat shock 70kDa protein A6(HSPA6), Hemoxygenase-1 (HO-1) , Matrix metalloproteinase-1 (MMP-1) , MMP-1, P63 immunostaining, Pro-MMP-1, Rodent inhalation studies, Tetrazolium salt resazurin, TGFβ1, Transforming growth factor β1, VITROCELL®

Cigarette 3R4F, Cigarette smoke