Application of a multi-layer systems toxicology framework for in vitro assessment of the biological effects of Classic Tobacco e-liquid and its corresponding aerosol using an e-cigarette device with MESH™ technology
Abstract:We previously proposed a systems toxicology framework for in vitro assessment of e-liquids. The framework starts with the first layer aimed at screening the potential toxicity of e-liquids, followed by the second layer aimed at investigating the toxicity-related mechanism of e-liquids, and finally, the third layer aimed at evaluating the toxicity-related mechanism of the corresponding aerosols. In this work, we applied this framework to assess the impact of the e-liquid MESH Classic Tobacco and its aerosol com… Show more
“…A specific point of consistency between the effects of Base ECV on human immature and LPS-matured MoDCs in the present study, and on buccal epithelial cells in the study of Iskandar et al (Iskandar et al 2019) is that we observed upregulation of inflammatory signalling molecules at 30 min and 24 h and Iskandar et al observed upregulation of an inflammatory transcriptome at 4 h and 24 h. In addition, we observed upregulation by ECVE of the release of IL-6 (but not other cytokines) from LPS-matured DCs, and they observed increased release of IL-1α and IP-10 (but not other cytokines) by buccal cells in response to Base ECV. These different studies thus provide consistent evidence for mild pro-inflammatory effects of Base ECV.…”
Section: Discussionsupporting
confidence: 67%
“…This is consistent with some other studies that have compared the effects of CS and ECV on different cell types. In particular, Iskandar et al (Iskandar et al 2019) recently reported that, in a multi-layer toxicology system, E-liquid and E-vapour were less toxic to cultured airway epithelial cells than was CS. They found that the 'Base' E-liquid that is equivalent to that used in our study (containing the humectants propylene glycol and vegetable glycerin, plus nicotine), and MESH Classic Tobaccoflavoured E-liquid, showed similar levels of toxicity.…”
Section: Discussionmentioning
confidence: 99%
“…Although some studies have reported that CS and ECV have similar effects on various cell types (Chen et al 2019), others have found that the effects of CS are much more pronounced and deleterious than those of ECV (Husari et al 2016;Iskandar et al 2019;Taylor et al 2016). Therefore, in view of the critical role of DCs in immunity and the marked effects of CS on DCs, in the current study, the effects of ECV on the phenotype and function of DCs was investigated by creating an in vitro cell culture model using human moDCs.…”
Dendritic cells (DCs) are professional antigen presenting cells that play a critical role in bridging innate and adaptive immunity. Numerous studies have shown that tobacco constituents present in conventional cigarettes affect the phenotype and function of DCs; however, no studies have examined the effects of vapour from E-cigarettes on human DCs. Here, the effects of E-cigarette vapour extract (ECVE) on the phenotype and function of DCs were investigated by creating an in vitro cell culture model using human monocyte-derived DCs (MoDCs). Immature DCs were generated from peripheral blood monocytes and mature DCs were then produced by treatment with LPS or Poly I:C for 24 h. For LPS-matured DCs, 3% ECVE treatment slightly suppressed HLA-DR and CD86 expression, whereas 1% ECVE treatment enhanced IL-6 production. The overall expression of 29 signalling molecules and other cytoplasmic proteins (mainly associated with DC activation) was significantly upregulated in immature DCs by 1% ECVE, and in LPS-treated DCs by 3% ECVE. In particular, the condition that induced IL-6 production also upregulated MAPK pathway activation. These findings indicate that E-cigarette vapour moderately affects human DCs, but the effects are less pronounced than those reported for tobacco smoke.
“…A specific point of consistency between the effects of Base ECV on human immature and LPS-matured MoDCs in the present study, and on buccal epithelial cells in the study of Iskandar et al (Iskandar et al 2019) is that we observed upregulation of inflammatory signalling molecules at 30 min and 24 h and Iskandar et al observed upregulation of an inflammatory transcriptome at 4 h and 24 h. In addition, we observed upregulation by ECVE of the release of IL-6 (but not other cytokines) from LPS-matured DCs, and they observed increased release of IL-1α and IP-10 (but not other cytokines) by buccal cells in response to Base ECV. These different studies thus provide consistent evidence for mild pro-inflammatory effects of Base ECV.…”
Section: Discussionsupporting
confidence: 67%
“…This is consistent with some other studies that have compared the effects of CS and ECV on different cell types. In particular, Iskandar et al (Iskandar et al 2019) recently reported that, in a multi-layer toxicology system, E-liquid and E-vapour were less toxic to cultured airway epithelial cells than was CS. They found that the 'Base' E-liquid that is equivalent to that used in our study (containing the humectants propylene glycol and vegetable glycerin, plus nicotine), and MESH Classic Tobaccoflavoured E-liquid, showed similar levels of toxicity.…”
Section: Discussionmentioning
confidence: 99%
“…Although some studies have reported that CS and ECV have similar effects on various cell types (Chen et al 2019), others have found that the effects of CS are much more pronounced and deleterious than those of ECV (Husari et al 2016;Iskandar et al 2019;Taylor et al 2016). Therefore, in view of the critical role of DCs in immunity and the marked effects of CS on DCs, in the current study, the effects of ECV on the phenotype and function of DCs was investigated by creating an in vitro cell culture model using human moDCs.…”
Dendritic cells (DCs) are professional antigen presenting cells that play a critical role in bridging innate and adaptive immunity. Numerous studies have shown that tobacco constituents present in conventional cigarettes affect the phenotype and function of DCs; however, no studies have examined the effects of vapour from E-cigarettes on human DCs. Here, the effects of E-cigarette vapour extract (ECVE) on the phenotype and function of DCs were investigated by creating an in vitro cell culture model using human monocyte-derived DCs (MoDCs). Immature DCs were generated from peripheral blood monocytes and mature DCs were then produced by treatment with LPS or Poly I:C for 24 h. For LPS-matured DCs, 3% ECVE treatment slightly suppressed HLA-DR and CD86 expression, whereas 1% ECVE treatment enhanced IL-6 production. The overall expression of 29 signalling molecules and other cytoplasmic proteins (mainly associated with DC activation) was significantly upregulated in immature DCs by 1% ECVE, and in LPS-treated DCs by 3% ECVE. In particular, the condition that induced IL-6 production also upregulated MAPK pathway activation. These findings indicate that E-cigarette vapour moderately affects human DCs, but the effects are less pronounced than those reported for tobacco smoke.
“…Aerosol deposited mass per puff as well as nicotine and carbonyl concentrations are commonly used for e-cig dosimetry measurement (Adamson et al . 2017 ; Iskandar et al , 2019 ; Bishop et al 2019 ). Figure 3.…”
Section: Exposure Systems Used With Ali Airway Culturesmentioning
confidence: 99%
“…To adapt the conventional smoking robots for e-cig research, Vitrocell® VapeStarters are used for activating various ecig products and, therefore, have greatly expanded the range of tobacco products that can be tested with the systems. Aerosol deposited mass per puff as well as nicotine and carbonyl concentrations are commonly used for e-cig dosimetry measurement (Adamson et al 2017;Iskandar et al, 2019;Bishop et al 2019).…”
Section: Exposure Systems Used With Ali Airway Culturesmentioning
Electronic nicotine delivery systems (ENDS) are being developed as potentially reduced-risk alternatives to the continued use of combustible tobacco products. Because of the widespread uptake of ENDS-in particular, e-cigarettes-the biological effects, including the toxic potential, of their aerosols are under investigation. Preclinically, collection of such aerosols is a prerequisite for testing in submerged cell culture-based in vitro assays; however, despite the growth in this research area, there is no apparent standardized collection method for this application. To this end, through an Institute for in vitro Sciences, Inc. workshop initiative, we surveyed the biomedical literature catalogued in PubMed® to map the types of methods hitherto used and reported publicly. From the 47 relevant publications retrieved, we identified seven distinct collection methods. Bubble-through (with aqueous solvents) and Cambridge filter pad (CFP) (with polar solvents) collection were the most frequently cited methods (57% and 18%, respectively), while the five others (CFP + bubble-through; condensation; cotton filters; settle-upon; settle-upon + dry) were cited less often (2-10%). Critically, the collected aerosol fractions were generally found to be only minimally characterized chemically, if at all. Furthermore, there was large heterogeneity among other experimental parameters (e.g., vaping regimen). Consequently, we recommend that more comprehensive research be conducted to identify the method(s) that produce the fraction(s) most representative of the native aerosol. We also endorse standardization of the aerosol generation process. These should be regarded as opportunities for increasing the value of in vitro assessments in relation to predicting effects on human health. K E Y W O R D S aerosol collection, e-cigarette, in vitro assays, literature survey, submerged cell cultures 1 | INTRODUCTION Electronic nicotine delivery systems (ENDS) are being developed as potentially reduced-risk alternatives to the continued use of combustible tobacco products (Brandon et al., 2015; Farsalinos & Polosa, 2014). Electronic cigarettes (e-cigarettes)-one of the most widely known ENDS-consist of a battery-powered device that heats an "e-liquid" contained inside an atomizer, which leads to generation
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