An investigation into E-cigarette cytotoxicity in-vitro using a novel 3D differentiated co-culture model of human airways

Pranav Vasanthi Bathri Narayanan, James E Brown, Lindsay Marshall, Laura J Leslie

Research output: Contribution to journalArticle

Abstract

Currently there is a lack of consensus on the possible adverse health effects of E-cigarettes (ECs). Important factors including cell model employed and exposure method determine the physiological relevance of EC studies. The present study aimed to evaluate EC cytotoxicity using a physiologically relevant in-vitro multicellular model of human airways.
Human bronchial epithelial cells (CALU-3) and pulmonary fibroblasts (MRC-5) were co-cultured at air-liquid-interface for 11-14 days post which they were exposed to whole cigarette smoke (WCS) or EC vapour (ECV) at standard ISO-3308 regime for 7 m using a bespoke aerosol delivery system. ECV effects were further investigated at higher exposure times (1 h – 6 h).
Results showed that while WCS significantly reduced cell viability after 7 m, ECV decreased cell viability only at exposure times higher than 3 h. Furthermore, ECV caused elevated IL-6 and IL-8 production despite reduced cell viability. ECV exposure also produced a marked increase in oxidative stress. Finally, WCS but not ECV exposure induced caspase 3/7 activation, suggesting a caspase independent death of ECV exposed cells.
Overall, our results indicate that prolonged ECV exposure (≥ 3 h) has a significant impact on pro-inflammatory mediators’ production, oxidative stress and cell viability but not caspase 3/7 activity.
LanguageEnglish
Pages255-264
JournalToxicology in Vitro
Volume52
Early online date27 Jun 2018
DOIs
Publication statusE-pub ahead of print - 27 Jun 2018

Fingerprint

Cytotoxicity
Coculture Techniques
Tobacco Products
Cell Survival
Vapors
Smoke
Caspase 7
Caspase 3
Oxidative Stress
Cells
Oxidative stress
Caspases
Aerosols
Interleukin-8
Interleukin-6
Fibroblasts
Epithelial Cells
Air
Lung
In Vitro Techniques

Bibliographical note

© 2018, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

  • E-cigarette
  • Cytotoxicity
  • Co-culture model
  • Human airways
  • Multi-cellular
  • CALU 3
  • In-vitro

Cite this

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abstract = "Currently there is a lack of consensus on the possible adverse health effects of E-cigarettes (ECs). Important factors including cell model employed and exposure method determine the physiological relevance of EC studies. The present study aimed to evaluate EC cytotoxicity using a physiologically relevant in-vitro multicellular model of human airways. Human bronchial epithelial cells (CALU-3) and pulmonary fibroblasts (MRC-5) were co-cultured at air-liquid-interface for 11-14 days post which they were exposed to whole cigarette smoke (WCS) or EC vapour (ECV) at standard ISO-3308 regime for 7 m using a bespoke aerosol delivery system. ECV effects were further investigated at higher exposure times (1 h – 6 h). Results showed that while WCS significantly reduced cell viability after 7 m, ECV decreased cell viability only at exposure times higher than 3 h. Furthermore, ECV caused elevated IL-6 and IL-8 production despite reduced cell viability. ECV exposure also produced a marked increase in oxidative stress. Finally, WCS but not ECV exposure induced caspase 3/7 activation, suggesting a caspase independent death of ECV exposed cells. Overall, our results indicate that prolonged ECV exposure (≥ 3 h) has a significant impact on pro-inflammatory mediators’ production, oxidative stress and cell viability but not caspase 3/7 activity.",
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An investigation into E-cigarette cytotoxicity in-vitro using a novel 3D differentiated co-culture model of human airways. / Vasanthi Bathri Narayanan, Pranav; Brown, James E; Marshall, Lindsay; Leslie, Laura J.

In: Toxicology in Vitro , Vol. 52, 27.06.2018, p. 255-264.

Research output: Contribution to journalArticle

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