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Persistent Inflammation and Nitric Oxide Dysregulation Are Transcriptomic Blueprints of Subglottic Stenosis
Subglottic stenosis (SGS) is a recurrent, obstructive, fibroinflammatory disease of the upper airway resulting in severe dyspnea, dysphonia, as well as other potentially fatal complications. Although aberrant inflammation and wound-healing are commonly associated with pathogenesis, the mechanism thr...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720859/ https://www.ncbi.nlm.nih.gov/pubmed/34987502 http://dx.doi.org/10.3389/fimmu.2021.748533 |
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author | Nguyen, Hoang C. B. Chao, Tiffany N. Cohen, Noam A. Mirza, Natasha |
author_facet | Nguyen, Hoang C. B. Chao, Tiffany N. Cohen, Noam A. Mirza, Natasha |
author_sort | Nguyen, Hoang C. B. |
collection | PubMed |
description | Subglottic stenosis (SGS) is a recurrent, obstructive, fibroinflammatory disease of the upper airway resulting in severe dyspnea, dysphonia, as well as other potentially fatal complications. Although aberrant inflammation and wound-healing are commonly associated with pathogenesis, the mechanism through which such processes occur and recur in affected patients remains poorly studied. Here we report that transcriptomic profiling of laryngotracheal regions from minimally-invasive mucosal swabs of SGS patients reveals a distinctively pro-inflammatory gene signature. Surprisingly, comparative genomics between SGS patients and mice with direct laryngotracheal injury suggest that SGS patients bear more resemblance to the acute than chronic phase of injury. Furthermore, functional and regulatory network analyses identify neutrophilic involvement through hyper-activation of NF-κB and its downstream inflammasome as a potential master regulator. Interestingly, nitric oxide synthesis was found to be downregulated in SGS patients compared to healthy controls. Thus, SGS represents a state of immunodeficiency whereby defective immune clearance triggers recurrent, long-lasting production of pro-inflammatory cytokines. |
format | Online Article Text |
id | pubmed-8720859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87208592022-01-04 Persistent Inflammation and Nitric Oxide Dysregulation Are Transcriptomic Blueprints of Subglottic Stenosis Nguyen, Hoang C. B. Chao, Tiffany N. Cohen, Noam A. Mirza, Natasha Front Immunol Immunology Subglottic stenosis (SGS) is a recurrent, obstructive, fibroinflammatory disease of the upper airway resulting in severe dyspnea, dysphonia, as well as other potentially fatal complications. Although aberrant inflammation and wound-healing are commonly associated with pathogenesis, the mechanism through which such processes occur and recur in affected patients remains poorly studied. Here we report that transcriptomic profiling of laryngotracheal regions from minimally-invasive mucosal swabs of SGS patients reveals a distinctively pro-inflammatory gene signature. Surprisingly, comparative genomics between SGS patients and mice with direct laryngotracheal injury suggest that SGS patients bear more resemblance to the acute than chronic phase of injury. Furthermore, functional and regulatory network analyses identify neutrophilic involvement through hyper-activation of NF-κB and its downstream inflammasome as a potential master regulator. Interestingly, nitric oxide synthesis was found to be downregulated in SGS patients compared to healthy controls. Thus, SGS represents a state of immunodeficiency whereby defective immune clearance triggers recurrent, long-lasting production of pro-inflammatory cytokines. Frontiers Media S.A. 2021-12-20 /pmc/articles/PMC8720859/ /pubmed/34987502 http://dx.doi.org/10.3389/fimmu.2021.748533 Text en Copyright © 2021 Nguyen, Chao, Cohen and Mirza https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Nguyen, Hoang C. B. Chao, Tiffany N. Cohen, Noam A. Mirza, Natasha Persistent Inflammation and Nitric Oxide Dysregulation Are Transcriptomic Blueprints of Subglottic Stenosis |
title | Persistent Inflammation and Nitric Oxide Dysregulation Are Transcriptomic Blueprints of Subglottic Stenosis |
title_full | Persistent Inflammation and Nitric Oxide Dysregulation Are Transcriptomic Blueprints of Subglottic Stenosis |
title_fullStr | Persistent Inflammation and Nitric Oxide Dysregulation Are Transcriptomic Blueprints of Subglottic Stenosis |
title_full_unstemmed | Persistent Inflammation and Nitric Oxide Dysregulation Are Transcriptomic Blueprints of Subglottic Stenosis |
title_short | Persistent Inflammation and Nitric Oxide Dysregulation Are Transcriptomic Blueprints of Subglottic Stenosis |
title_sort | persistent inflammation and nitric oxide dysregulation are transcriptomic blueprints of subglottic stenosis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720859/ https://www.ncbi.nlm.nih.gov/pubmed/34987502 http://dx.doi.org/10.3389/fimmu.2021.748533 |
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