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Toxicol In Vitro. 2018 Oct;52:255-264. doi: 10.1016/j.tiv.2018.06.020. Epub 2018 Jun 27.

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

Author information

1
Aston Institute of Materials Research, School of Engineering and Applied Science, Aston University, Birmingham B4 7ET, United Kingdom.
2
School of Life and Health Sciences, Aston University, Birmingham B4 7ET, United Kingdom; Aston Medical Research Institute, Aston University, Birmingham B4 7ET, United Kingdom.
3
Research and Toxicology Department, Humane Society International, 5, Underwood Street, London, United Kingdom.
4
Aston Institute of Materials Research, School of Engineering and Applied Science, Aston University, Birmingham B4 7ET, United Kingdom. Electronic address: l.j.leslie@aston.ac.uk.

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.

KEYWORDS:

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

PMID:
29940344
DOI:
10.1016/j.tiv.2018.06.020
[Indexed for MEDLINE]

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