ArticleAmerican journal of respiratory cell and molecular biology2014
Diacetyl induces amphiregulin shedding in pulmonary epithelial cells and in experimental bronchiolitis obliterans.
Article in American journal of respiratory cell and molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Targeting integrin beta 4 in diacetyl-induced anoikis of the airway epithelium.Cell death discovery · 2026Article
- CIP2A promotes bronchiolitis obliterans by activating the NF‑κB pathway.Molecular medicine reports · 2025Article
- Single-cell resolution of human airway epithelial cells exposed to bronchiolitis obliterans-associated chemicals.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- New insights on the potential effect of progesterone in Covid-19: Anti-inflammatory and immunosuppressive effects.Immunity, inflammation and disease · 2023Review
- Diacetyl inhalation impairs airway epithelial repair in mice infected with influenza A virus.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Post-translational modifications to hemidesmosomes in human airway epithelial cells following diacetyl exposure.Scientific reports · 2022Article
- E-cigarette and food flavoring diacetyl alters airway cell morphology, inflammatory and antiviral response, and susceptibility to SARS-CoV-2.Cell death discovery · 2022Article
- Repetitive diacetyl vapor exposure promotes ubiquitin proteasome stress and precedes bronchiolitis obliterans pathology.Archives of toxicology · 2021Article
- Invited review: human air-liquid-interface organotypic airway tissue models derived from primary tracheobronchial epithelial cells-overview and perspectives.In vitro cellular & developmental biology. Animal · 2021Review
- Acute cytotoxicity and increased vascular endothelial growth factor after in vitro nitrogen mustard vapor exposure.Annals of the New York Academy of Sciences · 2020Article
- Airway basal cell injury after acute diacetyl (2,3-butanedione) vapor exposure.Toxicology letters · 2020Article
- Amphiregulin contributes to airway remodeling in chronic allograft dysfunction after lung transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Article
- Postinfectious Bronchiolitis Obliterans in Children: Diagnostic Workup and Therapeutic Options: A Workshop Report.Canadian respiratory journal · 2020Review
- Production of amphiregulin and recovery from influenza is greater in males than females.Biology of sex differences · 2018Article
- Article
- Models of toxicity of diacetyl and alternative diones.Toxicology · 2017Review
- The Diacetyl-Exposed Human Airway Epithelial Secretome: New Insights into Flavoring-Induced Airways Disease.American journal of respiratory cell and molecular biology · 2017Article
- Proteomic Analysis of Primary Human Airway Epithelial Cells Exposed to the Respiratory Toxicant Diacetyl.Journal of proteome research · 2017Article
- Post-injury and resolution response to repetitive inhalation exposure to agricultural organic dust in mice.Safety (Basel, Switzerland) · 2017Article
- Progesterone-Based Therapy Protects Against Influenza by Promoting Lung Repair and Recovery in Females.PLoS pathogens · 2016Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Diacetyl (DA), a component of artificial butter flavoring, has been linked to the development of bronchiolitis obliterans (BO), a disease of airway epithelial injury and airway fibrosis. The epidermal growth factor receptor ligand, amphiregulin (AREG), has been implicated in other types of epithelial injury and lung fibrosis. We investigated the effects of DA directly on the pulmonary epithelium, and we hypothesized that DA exposure would result in epithelial cell shedding of AREG. Consistent with this hypothesis, we demonstrate that DA increases AREG by the pulmonary epithelial cell line NCI-H292 and by multiple independent primary human airway epithelial donors grown under physiologically relevant conditions at the air-liquid interface. Furthermore, we demonstrate that AREG shedding occurs through a TNF-α-converting enzyme (TACE)-dependent mechanism via inhibition of TACE activity in epithelial cells using the small molecule inhibitor, TNF-α protease inhibitor-1, as well as TACE-specific small inhibitor RNA. Finally, we demonstrate supportive in vivo results showing increased AREG transcript and protein levels in the lungs of rodents with DA-induced BO. In summary, our novel in vitro and in vivo observations suggest that further study of AREG is warranted in the pathogenesis of DA-induced BO.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.