E-cigarette and food flavoring diacetyl alters airway cell morphology, inflammatory and antiviral response, and susceptibility to SARS-CoV-2

Summary Diacetyl (DA) is an α-diketone that is used to flavor microwave popcorn, coffee, and e-cigarettes. Occupational exposure to high levels of DA causes impaired lung function and obstructive airway disease. Additionally, lower levels of DA exposure dampen host defenses in vitro. Understanding D...

Full description

Bibliographic Details
Main Authors: Stephanie N. Langel, Francine L. Kelly, David M. Brass, Andrew E. Nagler, Dylan Carmack, Joshua J. Tu, Tatianna Travieso, Ria Goswami, Sallie R. Permar, Maria Blasi, Scott M. Palmer
Format: Article
Language:English
Published: Nature Publishing Group 2022-02-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-022-00855-3
_version_ 1818280234988863488
author Stephanie N. Langel
Francine L. Kelly
David M. Brass
Andrew E. Nagler
Dylan Carmack
Joshua J. Tu
Tatianna Travieso
Ria Goswami
Sallie R. Permar
Maria Blasi
Scott M. Palmer
author_facet Stephanie N. Langel
Francine L. Kelly
David M. Brass
Andrew E. Nagler
Dylan Carmack
Joshua J. Tu
Tatianna Travieso
Ria Goswami
Sallie R. Permar
Maria Blasi
Scott M. Palmer
author_sort Stephanie N. Langel
collection DOAJ
description Summary Diacetyl (DA) is an α-diketone that is used to flavor microwave popcorn, coffee, and e-cigarettes. Occupational exposure to high levels of DA causes impaired lung function and obstructive airway disease. Additionally, lower levels of DA exposure dampen host defenses in vitro. Understanding DA’s impact on lung epithelium is important for delineating exposure risk on lung health. In this study, we assessed the impact of DA on normal human bronchial epithelial cell (NHBEC) morphology, transcriptional profiles, and susceptibility to SARS-CoV-2 infection. Transcriptomic analysis demonstrated cilia dysregulation, an increase in hypoxia and sterile inflammation associated pathways, and decreased expression of interferon-stimulated genes after DA exposure. Additionally, DA exposure resulted in cilia loss and increased hyaluronan production. After SARS-CoV-2 infection, both genomic and subgenomic SARS-CoV-2 RNA were increased in DA vapor- compared to vehicle-exposed NHBECs. This work suggests that transcriptomic and physiologic changes induced by DA vapor exposure damage cilia and increase host susceptibility to SARS-CoV-2.
first_indexed 2024-12-12T23:46:00Z
format Article
id doaj.art-646ba4f0dd024f46b2eed9d2d8ac948a
institution Directory Open Access Journal
issn 2058-7716
language English
last_indexed 2024-12-12T23:46:00Z
publishDate 2022-02-01
publisher Nature Publishing Group
record_format Article
series Cell Death Discovery
spelling doaj.art-646ba4f0dd024f46b2eed9d2d8ac948a2022-12-22T00:06:51ZengNature Publishing GroupCell Death Discovery2058-77162022-02-018111110.1038/s41420-022-00855-3E-cigarette and food flavoring diacetyl alters airway cell morphology, inflammatory and antiviral response, and susceptibility to SARS-CoV-2Stephanie N. Langel0Francine L. Kelly1David M. Brass2Andrew E. Nagler3Dylan Carmack4Joshua J. Tu5Tatianna Travieso6Ria Goswami7Sallie R. Permar8Maria Blasi9Scott M. Palmer10Duke Center for Human Systems Immunology and Department of SurgeryDuke Clinical Research Institute and Department of Medicine, Duke University Medical CenterDuke Clinical Research Institute and Department of Medicine, Duke University Medical CenterDuke Clinical Research Institute and Department of Medicine, Duke University Medical CenterDuke Clinical Research Institute and Department of Medicine, Duke University Medical CenterDuke Human Vaccine Institute, Duke University Medical CenterDuke Human Vaccine Institute, Duke University Medical CenterDepartment of Pediatrics, Weill Cornell MedicineDepartment of Pediatrics, Weill Cornell MedicineDuke Human Vaccine Institute, Duke University Medical CenterDuke Clinical Research Institute and Department of Medicine, Duke University Medical CenterSummary Diacetyl (DA) is an α-diketone that is used to flavor microwave popcorn, coffee, and e-cigarettes. Occupational exposure to high levels of DA causes impaired lung function and obstructive airway disease. Additionally, lower levels of DA exposure dampen host defenses in vitro. Understanding DA’s impact on lung epithelium is important for delineating exposure risk on lung health. In this study, we assessed the impact of DA on normal human bronchial epithelial cell (NHBEC) morphology, transcriptional profiles, and susceptibility to SARS-CoV-2 infection. Transcriptomic analysis demonstrated cilia dysregulation, an increase in hypoxia and sterile inflammation associated pathways, and decreased expression of interferon-stimulated genes after DA exposure. Additionally, DA exposure resulted in cilia loss and increased hyaluronan production. After SARS-CoV-2 infection, both genomic and subgenomic SARS-CoV-2 RNA were increased in DA vapor- compared to vehicle-exposed NHBECs. This work suggests that transcriptomic and physiologic changes induced by DA vapor exposure damage cilia and increase host susceptibility to SARS-CoV-2.https://doi.org/10.1038/s41420-022-00855-3
spellingShingle Stephanie N. Langel
Francine L. Kelly
David M. Brass
Andrew E. Nagler
Dylan Carmack
Joshua J. Tu
Tatianna Travieso
Ria Goswami
Sallie R. Permar
Maria Blasi
Scott M. Palmer
E-cigarette and food flavoring diacetyl alters airway cell morphology, inflammatory and antiviral response, and susceptibility to SARS-CoV-2
Cell Death Discovery
title E-cigarette and food flavoring diacetyl alters airway cell morphology, inflammatory and antiviral response, and susceptibility to SARS-CoV-2
title_full E-cigarette and food flavoring diacetyl alters airway cell morphology, inflammatory and antiviral response, and susceptibility to SARS-CoV-2
title_fullStr E-cigarette and food flavoring diacetyl alters airway cell morphology, inflammatory and antiviral response, and susceptibility to SARS-CoV-2
title_full_unstemmed E-cigarette and food flavoring diacetyl alters airway cell morphology, inflammatory and antiviral response, and susceptibility to SARS-CoV-2
title_short E-cigarette and food flavoring diacetyl alters airway cell morphology, inflammatory and antiviral response, and susceptibility to SARS-CoV-2
title_sort e cigarette and food flavoring diacetyl alters airway cell morphology inflammatory and antiviral response and susceptibility to sars cov 2
url https://doi.org/10.1038/s41420-022-00855-3
work_keys_str_mv AT stephanienlangel ecigaretteandfoodflavoringdiacetylaltersairwaycellmorphologyinflammatoryandantiviralresponseandsusceptibilitytosarscov2
AT francinelkelly ecigaretteandfoodflavoringdiacetylaltersairwaycellmorphologyinflammatoryandantiviralresponseandsusceptibilitytosarscov2
AT davidmbrass ecigaretteandfoodflavoringdiacetylaltersairwaycellmorphologyinflammatoryandantiviralresponseandsusceptibilitytosarscov2
AT andrewenagler ecigaretteandfoodflavoringdiacetylaltersairwaycellmorphologyinflammatoryandantiviralresponseandsusceptibilitytosarscov2
AT dylancarmack ecigaretteandfoodflavoringdiacetylaltersairwaycellmorphologyinflammatoryandantiviralresponseandsusceptibilitytosarscov2
AT joshuajtu ecigaretteandfoodflavoringdiacetylaltersairwaycellmorphologyinflammatoryandantiviralresponseandsusceptibilitytosarscov2
AT tatiannatravieso ecigaretteandfoodflavoringdiacetylaltersairwaycellmorphologyinflammatoryandantiviralresponseandsusceptibilitytosarscov2
AT riagoswami ecigaretteandfoodflavoringdiacetylaltersairwaycellmorphologyinflammatoryandantiviralresponseandsusceptibilitytosarscov2
AT sallierpermar ecigaretteandfoodflavoringdiacetylaltersairwaycellmorphologyinflammatoryandantiviralresponseandsusceptibilitytosarscov2
AT mariablasi ecigaretteandfoodflavoringdiacetylaltersairwaycellmorphologyinflammatoryandantiviralresponseandsusceptibilitytosarscov2
AT scottmpalmer ecigaretteandfoodflavoringdiacetylaltersairwaycellmorphologyinflammatoryandantiviralresponseandsusceptibilitytosarscov2