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Dysregulated repair and inflammatory responses by e‐cigarette‐derived inhaled nicotine and humectant propylene glycol in a sex‐dependent manner in mouse lung

Nicotine inhalation via electronic cigarettes (e‐cigs) is an emerging concern. However, little is known about the acute toxicity in the lungs following inhalation of nicotine‐containing e‐cig aerosols. We hypothesized that acute exposure to aerosolized nicotine causes lung toxicity by eliciting infl...

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Autores principales: Wang, Qixin, Ahmad Khan, Naushad, Muthumalage, Thivanka, Lawyer, Gina R., McDonough, Samantha R., Chuang, Tsai‐Der, Gong, Ming, Sundar, Isaac K., Rehan, Virender K., Rahman, Irfan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902908/
https://www.ncbi.nlm.nih.gov/pubmed/31825014
http://dx.doi.org/10.1096/fba.2019-00048
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author Wang, Qixin
Ahmad Khan, Naushad
Muthumalage, Thivanka
Lawyer, Gina R.
McDonough, Samantha R.
Chuang, Tsai‐Der
Gong, Ming
Sundar, Isaac K.
Rehan, Virender K.
Rahman, Irfan
author_facet Wang, Qixin
Ahmad Khan, Naushad
Muthumalage, Thivanka
Lawyer, Gina R.
McDonough, Samantha R.
Chuang, Tsai‐Der
Gong, Ming
Sundar, Isaac K.
Rehan, Virender K.
Rahman, Irfan
author_sort Wang, Qixin
collection PubMed
description Nicotine inhalation via electronic cigarettes (e‐cigs) is an emerging concern. However, little is known about the acute toxicity in the lungs following inhalation of nicotine‐containing e‐cig aerosols. We hypothesized that acute exposure to aerosolized nicotine causes lung toxicity by eliciting inflammatory and dysregulated repair responses. Adult C57BL/6J mice were exposed 2 hours daily for 3 days to e‐cig aerosols containing propylene glycol (PG) with or without nicotine. Acute exposure to nicotine‐containing e‐cig aerosols induced inflammatory cell influx (neutrophils and CD8a(+) T lymphocytes), and release of pro‐inflammatory cytokines in bronchoalveolar lavage fluid in a sex‐dependent manner. Inhalation of e‐cig aerosol containing PG alone significantly augmented the lung levels of various homeostasis/repair mediators (PPARγ, ADRP, ACTA2, CTNNB1, LEF1, β‐catenin, E‐cadherin, and MMP2) in a sex‐dependent manner when compared to air controls. These findings were accompanied by an increase in protein abundance and altered gene expression of lipogenic markers (PPARγ, ADRP) and myogenic markers (fibronectin, α‐smooth muscle actin and β‐catenin), suggesting a dysregulated repair response in mouse lungs. Furthermore, exposure to nicotine‐containing e‐cig aerosols or PG alone differentially affected the release of pro‐inflammatory cytokines in healthy and COPD human 3D EpiAirway tissues. Overall, acute exposure to nicotine‐containing e‐cig aerosols was sufficient to elicit a pro‐inflammatory response and altered mRNA and protein levels of myogenic, lipogenic, and extracellular matrix markers in mouse lung in a sex‐dependent manner. Thus, acute exposure to inhaled nicotine via e‐cig leads to dysregulated repair and inflammatory responses, which may lead to airway remodeling in the lungs.
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spelling pubmed-69029082020-03-02 Dysregulated repair and inflammatory responses by e‐cigarette‐derived inhaled nicotine and humectant propylene glycol in a sex‐dependent manner in mouse lung Wang, Qixin Ahmad Khan, Naushad Muthumalage, Thivanka Lawyer, Gina R. McDonough, Samantha R. Chuang, Tsai‐Der Gong, Ming Sundar, Isaac K. Rehan, Virender K. Rahman, Irfan FASEB Bioadv Research Articles Nicotine inhalation via electronic cigarettes (e‐cigs) is an emerging concern. However, little is known about the acute toxicity in the lungs following inhalation of nicotine‐containing e‐cig aerosols. We hypothesized that acute exposure to aerosolized nicotine causes lung toxicity by eliciting inflammatory and dysregulated repair responses. Adult C57BL/6J mice were exposed 2 hours daily for 3 days to e‐cig aerosols containing propylene glycol (PG) with or without nicotine. Acute exposure to nicotine‐containing e‐cig aerosols induced inflammatory cell influx (neutrophils and CD8a(+) T lymphocytes), and release of pro‐inflammatory cytokines in bronchoalveolar lavage fluid in a sex‐dependent manner. Inhalation of e‐cig aerosol containing PG alone significantly augmented the lung levels of various homeostasis/repair mediators (PPARγ, ADRP, ACTA2, CTNNB1, LEF1, β‐catenin, E‐cadherin, and MMP2) in a sex‐dependent manner when compared to air controls. These findings were accompanied by an increase in protein abundance and altered gene expression of lipogenic markers (PPARγ, ADRP) and myogenic markers (fibronectin, α‐smooth muscle actin and β‐catenin), suggesting a dysregulated repair response in mouse lungs. Furthermore, exposure to nicotine‐containing e‐cig aerosols or PG alone differentially affected the release of pro‐inflammatory cytokines in healthy and COPD human 3D EpiAirway tissues. Overall, acute exposure to nicotine‐containing e‐cig aerosols was sufficient to elicit a pro‐inflammatory response and altered mRNA and protein levels of myogenic, lipogenic, and extracellular matrix markers in mouse lung in a sex‐dependent manner. Thus, acute exposure to inhaled nicotine via e‐cig leads to dysregulated repair and inflammatory responses, which may lead to airway remodeling in the lungs. John Wiley and Sons Inc. 2019-09-13 /pmc/articles/PMC6902908/ /pubmed/31825014 http://dx.doi.org/10.1096/fba.2019-00048 Text en © 2019 The Authors. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Wang, Qixin
Ahmad Khan, Naushad
Muthumalage, Thivanka
Lawyer, Gina R.
McDonough, Samantha R.
Chuang, Tsai‐Der
Gong, Ming
Sundar, Isaac K.
Rehan, Virender K.
Rahman, Irfan
Dysregulated repair and inflammatory responses by e‐cigarette‐derived inhaled nicotine and humectant propylene glycol in a sex‐dependent manner in mouse lung
title Dysregulated repair and inflammatory responses by e‐cigarette‐derived inhaled nicotine and humectant propylene glycol in a sex‐dependent manner in mouse lung
title_full Dysregulated repair and inflammatory responses by e‐cigarette‐derived inhaled nicotine and humectant propylene glycol in a sex‐dependent manner in mouse lung
title_fullStr Dysregulated repair and inflammatory responses by e‐cigarette‐derived inhaled nicotine and humectant propylene glycol in a sex‐dependent manner in mouse lung
title_full_unstemmed Dysregulated repair and inflammatory responses by e‐cigarette‐derived inhaled nicotine and humectant propylene glycol in a sex‐dependent manner in mouse lung
title_short Dysregulated repair and inflammatory responses by e‐cigarette‐derived inhaled nicotine and humectant propylene glycol in a sex‐dependent manner in mouse lung
title_sort dysregulated repair and inflammatory responses by e‐cigarette‐derived inhaled nicotine and humectant propylene glycol in a sex‐dependent manner in mouse lung
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902908/
https://www.ncbi.nlm.nih.gov/pubmed/31825014
http://dx.doi.org/10.1096/fba.2019-00048
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