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Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model

The use of electronic nicotine delivery systems (ENDS), also known as electronic-cigarettes (e-cigs), has raised serious public health concerns, especially in light of the 2019 outbreak of e-cig or vaping product use-associated acute lung injury (EVALI). While these cases have mostly been linked to...

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Autores principales: Szafran, Brittany N., Pinkston, Rakeysha, Perveen, Zakia, Ross, Matthew K., Morgan, Timothy, Paulsen, Daniel B., Penn, Arthur L., Kaplan, Barbara L. F., Noël, Alexandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504509/
https://www.ncbi.nlm.nih.gov/pubmed/32825651
http://dx.doi.org/10.3390/ijms21176022
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author Szafran, Brittany N.
Pinkston, Rakeysha
Perveen, Zakia
Ross, Matthew K.
Morgan, Timothy
Paulsen, Daniel B.
Penn, Arthur L.
Kaplan, Barbara L. F.
Noël, Alexandra
author_facet Szafran, Brittany N.
Pinkston, Rakeysha
Perveen, Zakia
Ross, Matthew K.
Morgan, Timothy
Paulsen, Daniel B.
Penn, Arthur L.
Kaplan, Barbara L. F.
Noël, Alexandra
author_sort Szafran, Brittany N.
collection PubMed
description The use of electronic nicotine delivery systems (ENDS), also known as electronic-cigarettes (e-cigs), has raised serious public health concerns, especially in light of the 2019 outbreak of e-cig or vaping product use-associated acute lung injury (EVALI). While these cases have mostly been linked to ENDS that contain vitamin E acetate, there is limited research that has focused on the chronic pulmonary effects of the delivery vehicles (i.e., without nicotine and flavoring). Thus, we investigated lung function and immune responses in a mouse model following exposure to the nearly ubiquitous e-cig delivery vehicles, vegetable glycerin (VG) and propylene glycol (PG), used with a specific 70%/30% ratio, with or without vanilla flavoring. We hypothesized that mice exposed sub-acutely to these e-cig aerosols would exhibit lung inflammation and altered lung function. Adult female C57BL/6 mice (n = 11–12 per group) were exposed to filtered air, 70%/30% VG/PG, or 70%/30% VG/PG with a French vanilla flavoring for 2 h a day for 6 weeks. Prior to sacrifice, lung function was assessed. At sacrifice, broncho-alveolar lavage fluid and lung tissue were collected for lipid mediator analysis, flow cytometry, histopathology, and gene expression analyses. Exposures to VG/PG + vanilla e-cig aerosol increased lung tidal and minute volumes and tissue damping. Immunophenotyping of lung immune cells revealed an increased number of dendritic cells, CD4+ T cells, and CD19+ B cells in the VG/PG-exposed group compared to air, irrespective of the presence of vanilla flavoring. Quantification of bioactive lung lipids demonstrated a >3-fold increase of 2-arachidonoylglycerol (2-AG), an anti-inflammatory mediator, and a 2-fold increase of 12-hydroxyeicosatetraenoic acid (12-HETE), another inflammatory mediator, following VG/PG exposure, with or without vanilla flavoring. This suggests that e-cig aerosol vehicles may affect immunoregulatory molecules. We also found that the two e-cig aerosols dysregulated the expression of lung genes. Ingenuity Pathway Analysis revealed that the gene networks that are dysregulated by the VG/PG e-cig aerosol are associated with metabolism of cellular proteins and lipids. Overall, our findings demonstrate that VG and PG, the main constituents of e-liquid formulations, when aerosolized through an e-cig device, are not harmless to the lungs, since they disrupt immune homeostasis.
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spelling pubmed-75045092020-09-24 Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model Szafran, Brittany N. Pinkston, Rakeysha Perveen, Zakia Ross, Matthew K. Morgan, Timothy Paulsen, Daniel B. Penn, Arthur L. Kaplan, Barbara L. F. Noël, Alexandra Int J Mol Sci Article The use of electronic nicotine delivery systems (ENDS), also known as electronic-cigarettes (e-cigs), has raised serious public health concerns, especially in light of the 2019 outbreak of e-cig or vaping product use-associated acute lung injury (EVALI). While these cases have mostly been linked to ENDS that contain vitamin E acetate, there is limited research that has focused on the chronic pulmonary effects of the delivery vehicles (i.e., without nicotine and flavoring). Thus, we investigated lung function and immune responses in a mouse model following exposure to the nearly ubiquitous e-cig delivery vehicles, vegetable glycerin (VG) and propylene glycol (PG), used with a specific 70%/30% ratio, with or without vanilla flavoring. We hypothesized that mice exposed sub-acutely to these e-cig aerosols would exhibit lung inflammation and altered lung function. Adult female C57BL/6 mice (n = 11–12 per group) were exposed to filtered air, 70%/30% VG/PG, or 70%/30% VG/PG with a French vanilla flavoring for 2 h a day for 6 weeks. Prior to sacrifice, lung function was assessed. At sacrifice, broncho-alveolar lavage fluid and lung tissue were collected for lipid mediator analysis, flow cytometry, histopathology, and gene expression analyses. Exposures to VG/PG + vanilla e-cig aerosol increased lung tidal and minute volumes and tissue damping. Immunophenotyping of lung immune cells revealed an increased number of dendritic cells, CD4+ T cells, and CD19+ B cells in the VG/PG-exposed group compared to air, irrespective of the presence of vanilla flavoring. Quantification of bioactive lung lipids demonstrated a >3-fold increase of 2-arachidonoylglycerol (2-AG), an anti-inflammatory mediator, and a 2-fold increase of 12-hydroxyeicosatetraenoic acid (12-HETE), another inflammatory mediator, following VG/PG exposure, with or without vanilla flavoring. This suggests that e-cig aerosol vehicles may affect immunoregulatory molecules. We also found that the two e-cig aerosols dysregulated the expression of lung genes. Ingenuity Pathway Analysis revealed that the gene networks that are dysregulated by the VG/PG e-cig aerosol are associated with metabolism of cellular proteins and lipids. Overall, our findings demonstrate that VG and PG, the main constituents of e-liquid formulations, when aerosolized through an e-cig device, are not harmless to the lungs, since they disrupt immune homeostasis. MDPI 2020-08-21 /pmc/articles/PMC7504509/ /pubmed/32825651 http://dx.doi.org/10.3390/ijms21176022 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Szafran, Brittany N.
Pinkston, Rakeysha
Perveen, Zakia
Ross, Matthew K.
Morgan, Timothy
Paulsen, Daniel B.
Penn, Arthur L.
Kaplan, Barbara L. F.
Noël, Alexandra
Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model
title Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model
title_full Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model
title_fullStr Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model
title_full_unstemmed Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model
title_short Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model
title_sort electronic-cigarette vehicles and flavoring affect lung function and immune responses in a murine model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504509/
https://www.ncbi.nlm.nih.gov/pubmed/32825651
http://dx.doi.org/10.3390/ijms21176022
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