Short-term whole body cigarette smoke exposure induces regional differences in cellular response in the mouse larynx
The larynx is an essential organ in the respiratory tract and necessary for airway protection, respiration, and phonation. Cigarette smoking is a significant risk factor associated with benign and malignant laryngeal diseases. Despite this association, the underlying mechanisms by which cigarette sm...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Toxicology Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214750021000834 |
| _version_ | 1819179208272773120 |
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| author | Meena Easwaran Joshua D. Martinez Daniel J. Ramirez Phillip A. Gall Elizabeth Erickson-DiRenzo |
| author_facet | Meena Easwaran Joshua D. Martinez Daniel J. Ramirez Phillip A. Gall Elizabeth Erickson-DiRenzo |
| author_sort | Meena Easwaran |
| collection | DOAJ |
| description | The larynx is an essential organ in the respiratory tract and necessary for airway protection, respiration, and phonation. Cigarette smoking is a significant risk factor associated with benign and malignant laryngeal diseases. Despite this association, the underlying mechanisms by which cigarette smoke (CS) drives disease development are not well elucidated. In the current study, we developed a short-term murine whole body inhalation model to evaluate the first CS-induced cellular responses in the glottic [i.e. vocal fold (VF)] and subglottic regions of the larynx. Specifically, we investigated epithelial cell proliferation, cell death, surface topography, and mucus production, at various time points (1 day, 5 days, 10 days) after ∼ 2 h exposure to 3R4F cigarettes (Delivered dose: 5.6968 mg/kg per cigarette) and following cessation for 5 days after a 5 day CS exposure (CSE). CSE elevated levels of BrdU labeled proliferative cells and p63 labeled epithelial basal cells on day 1 in the VF. CSE increased proliferative cells in the subglottis at days 5, 10 and following cessation in the subglottis. Cleaved caspase-3 apoptotic activity was absent in VF at all time points and increased at day 1 in the subglottis. Evaluation of the VF surface by scanning electron microscopy (SEM) revealed significant epithelial microprojection damage at day 10 and early signs of necrosis at days 5 and 10 post-CSE. SEM visualizations additionally indicated the presence of deformed cilia at days 5 and 10 after CSE and post-cessation in the respiratory epithelium lined subglottis. In terms of mucin content, the impact of short-term CSE was observed only at day 10, with decreasing acidic mucin levels and increasing neutral mucin levels. Overall, these findings reveal regional differences in murine laryngeal cellular responses following short-term CSE and provide insight into potential mechanisms underlying CS-induced laryngeal disease development. |
| first_indexed | 2024-12-22T21:54:47Z |
| format | Article |
| id | doaj.art-8ace75b1a1e3482cacca0732af49b78b |
| institution | Directory Open Access Journal |
| issn | 2214-7500 |
| language | English |
| last_indexed | 2024-12-22T21:54:47Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj.art-8ace75b1a1e3482cacca0732af49b78b2022-12-21T18:11:17ZengElsevierToxicology Reports2214-75002021-01-018920937Short-term whole body cigarette smoke exposure induces regional differences in cellular response in the mouse larynxMeena Easwaran0Joshua D. Martinez1Daniel J. Ramirez2Phillip A. Gall3Elizabeth Erickson-DiRenzo4Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USACorresponding author at: Division of Laryngology, Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, 94305-5739, USA.; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USAThe larynx is an essential organ in the respiratory tract and necessary for airway protection, respiration, and phonation. Cigarette smoking is a significant risk factor associated with benign and malignant laryngeal diseases. Despite this association, the underlying mechanisms by which cigarette smoke (CS) drives disease development are not well elucidated. In the current study, we developed a short-term murine whole body inhalation model to evaluate the first CS-induced cellular responses in the glottic [i.e. vocal fold (VF)] and subglottic regions of the larynx. Specifically, we investigated epithelial cell proliferation, cell death, surface topography, and mucus production, at various time points (1 day, 5 days, 10 days) after ∼ 2 h exposure to 3R4F cigarettes (Delivered dose: 5.6968 mg/kg per cigarette) and following cessation for 5 days after a 5 day CS exposure (CSE). CSE elevated levels of BrdU labeled proliferative cells and p63 labeled epithelial basal cells on day 1 in the VF. CSE increased proliferative cells in the subglottis at days 5, 10 and following cessation in the subglottis. Cleaved caspase-3 apoptotic activity was absent in VF at all time points and increased at day 1 in the subglottis. Evaluation of the VF surface by scanning electron microscopy (SEM) revealed significant epithelial microprojection damage at day 10 and early signs of necrosis at days 5 and 10 post-CSE. SEM visualizations additionally indicated the presence of deformed cilia at days 5 and 10 after CSE and post-cessation in the respiratory epithelium lined subglottis. In terms of mucin content, the impact of short-term CSE was observed only at day 10, with decreasing acidic mucin levels and increasing neutral mucin levels. Overall, these findings reveal regional differences in murine laryngeal cellular responses following short-term CSE and provide insight into potential mechanisms underlying CS-induced laryngeal disease development.http://www.sciencedirect.com/science/article/pii/S2214750021000834Cigarette smokeMurine larynxCell proliferationCell deathSurface topographyMucus production |
| spellingShingle | Meena Easwaran Joshua D. Martinez Daniel J. Ramirez Phillip A. Gall Elizabeth Erickson-DiRenzo Short-term whole body cigarette smoke exposure induces regional differences in cellular response in the mouse larynx Toxicology Reports Cigarette smoke Murine larynx Cell proliferation Cell death Surface topography Mucus production |
| title | Short-term whole body cigarette smoke exposure induces regional differences in cellular response in the mouse larynx |
| title_full | Short-term whole body cigarette smoke exposure induces regional differences in cellular response in the mouse larynx |
| title_fullStr | Short-term whole body cigarette smoke exposure induces regional differences in cellular response in the mouse larynx |
| title_full_unstemmed | Short-term whole body cigarette smoke exposure induces regional differences in cellular response in the mouse larynx |
| title_short | Short-term whole body cigarette smoke exposure induces regional differences in cellular response in the mouse larynx |
| title_sort | short term whole body cigarette smoke exposure induces regional differences in cellular response in the mouse larynx |
| topic | Cigarette smoke Murine larynx Cell proliferation Cell death Surface topography Mucus production |
| url | http://www.sciencedirect.com/science/article/pii/S2214750021000834 |
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