Walsh, P.T., Chalupowicz, D.G., Frankowski, R., Barnette, M. Discovery Biology, Respiratory CEDD, GlaxoSmithKline, Upper Merion, PA19406, USA.

This study by researchers at GlaxoSmithKline (GSK) demonstrated that MatTek’s EpiAirwayFT (“full thickness”) human airway in vitro tissue model is a more appropriate physiological model of lung parenchymal tissue than monolayer airway epithelial cell cultures for the analysis of the mechanisms associated with smoking related disease such as inflammation and tissue remodeling and repair. Rationale: Airway epithelial cells (AECs) represent the front line in terms of exposure to toxic stimuli contained in cigarette smoke. However it is becoming increasingly evident that the interaction of these cells with the extracellular matrix and other cell types resident in lung parenchymal tissue plays an integral role in mechanisms associated with smoking related disease such as inflammation and tissue remodeling and repair. In order to examine such mechanisms more closely, researchers at GlaxoSmithKline (GSK) examined the responses of an epithelial cell/fibroblast co-culture system (EpiAirwayFT, MatTek) to whole cigarette smoke using the Vitrocell system. Methods: As a model of full thickness airway tissue, AECs were cultured and differentiated at the air liquid interface (ALI) over a collagen matrix containing normal pulmonary fibroblasts. Co-cultured cells were exposed to diluted whole cigarette smoke (20%) or clean air for one hour duration using Vitrocell cell exposure chambers. Conditions mimicking acute (single) vs. chronic (repeated) smoke exposure were established. After the final exposure, cells were returned to ALI culture and basolateral medium was sampled over next 24-48 hours and examined for secreted cytokines, chemokines and growth factors using Luminex technology. Results: Repeated exposure of cells did not adversely affect viability, as measured by MTT uptake, and lead to a significant increase in the levels of secreted cytokines IL-6, IL-7 and GM-CSF, the chemokines IL-8, MCP-1, MIP-1á and the growth factors VEGF, HGF and G-CSF. In contrast, a single exposure to cigarette smoke was sufficient to lead to increased expression of IL-10 and decreased expression of the chemokine eotaxin. Conclusions: Co-culture of fully differentiated AECs on a collagen matrix containing primary pulmonary fibroblasts represents an appropriate physiological model of lung parenchymal tissue for the analysis of the effects of cigarette smoke exposure.


AFT-100-PC12, Acute exposure, Cigarette smoke, Eotaxin, EpiAirway-FT, G-CSG, GM-CSF, HGF, IL-10, IL-6, IL-7, IL-8, Inflammation, MCP-1, MIP-1a, Repeat exposure, TGF-b1, Tissue remodeling, Tissue repair, VEGF, Vitrocell

Materials Tested

Cigarette smoke

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