title: Evaluation of an air-liquid interface cell culture model for studies on the inflammatory and cytotoxic responses to tobacco smoke aerosols.
abstract: In vitro toxicological studies for tobacco product assessment have traditionally been undertaken using the particulate phase of tobacco smoke. However, this does not truly reflect exposure conditions that occur in smokers. Thus in vitro cell culture systems are required in which cells are exposed to tobacco whole smoke (WS) at the air-liquid interface (ALI). In this study bronchial epithelial cells were cultured on semi-permeable membranes, transitioned to the ALI and the robustness and sensitivity of the cells to tobacco WS and vapour phase (VP) assessed. Although no effect of air exposure was observed on cell viability, IL-6 and IL-8 release was increased. Exposure to WS resulted in a significant dose dependent decrease in cell viability and a significant non-dose dependent increase in inflammatory mediator secretion. The VP was found to contribute approximately 90% of the total cytotoxicity derived from WS. The cell culture system was also able to differentiate between two smoking regimens and was sensitive to passage number with increased inflammatory mediator secretion and lower cell viability observed in cell cultures of low passage number following WS exposure. This simple cell culture system may facilitate studies on the toxicological impact of future tobacco products and nicotine delivery devices.
authors.affiliation: British American Tobacco (Investments) Limited, Group R&D, Regents Park Road, Southampton SO15 8TL, UK.
authors.forename: David
authors.initials: D
authors.lastname: Azzopardi
authors.affiliation: British American Tobacco (Investments) Limited, Group R&D, Regents Park Road, Southampton SO15 8TL, UK.
authors.forename: Linsey E
authors.initials: LE
authors.lastname: Haswell
authors.affiliation: British American Tobacco (Investments) Limited, Group R&D, Regents Park Road, Southampton SO15 8TL, UK.
authors.forename: Geoff
authors.initials: G
authors.lastname: Foss-Smith
authors.affiliation: British American Tobacco (Investments) Limited, Group R&D, Regents Park Road, Southampton SO15 8TL, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Hewitt
authors.affiliation: British American Tobacco (Investments) Limited, Group R&D, Regents Park Road, Southampton SO15 8TL, UK.
authors.forename: Nathan
authors.initials: N
authors.lastname: Asquith
authors.affiliation: British American Tobacco (Investments) Limited, Group R&D, Regents Park Road, Southampton SO15 8TL, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Corke
authors.affiliation: British American Tobacco (Investments) Limited, Group R&D, Regents Park Road, Southampton SO15 8TL, UK. Electronic address: gary_phillips@bat.com.
authors.forename: Gary
authors.initials: G
authors.lastname: Phillips
mesh_terms: D000336:Aerosols; D000388:Air; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6; D016209:Interleukin-8; D020781:Matrix Metalloproteinase 1; D009499:Neutral Red / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
chemical_list: D000336:Aerosols; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D012906:Smoke; D009499:Neutral Red; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: Air–liquid interface; Cytotoxicity; In vitro; Inflammation; Lung; Tobacco