Airway Epithelial NF-κB Activation Modulates Asbestos-Induced Inflammation and Mucin Production In Vivo
Abstract
To investigate the role of bronchiolar epithelial NF-κB activity in the development of inflammation and fibrogenesis in a murine model of asbestos inhalation, we used transgenic (Tg) mice expressing an IκBα mutant (IκBαsr) resistant to phosphorylation-induced degradation and targeted to bronchial epithelium using the CC10 promoter. Sham and chrysotile asbestos-exposed CC10-IκBαsr Tg+ and Tg− mice were examined for altered epithelial cell proliferation and differentiation, cytokine profiles, lung inflammation, and fibrogenesis at 3, 9, and 40 days. KC, IL-6 and IL-1β were increased (p ≤ 0.05) in bronchoalveolar lavage fluid (BALF) from asbestos-exposed mice, but to a lesser extent (p ≤ 0.05) in Tg+ vs Tg− mice. Asbestos also caused increases in IL-4, MIP-1β, and MCP-1 in BALF that were more elevated (p ≤ 0.05) in Tg+ mice at 9 days. Differential cell counts revealed eosinophils in BALF that increased (p ≤ 0.05) in Tg+ mice at 9 days, a time point corresponding with significantly increased numbers of bronchiolar epithelial cells staining positively for mucus production. At all time points, asbestos caused increased numbers of distal bronchiolar epithelial cells and peribronchiolar cells incorporating the proliferation marker, Ki-67. However, bronchiolar epithelial cell and interstitial cell labeling was diminished at 40 days (p ≤ 0.05) in Tg+ vs Tg− mice. Our findings demonstrate that airway epithelial NF-κB activity plays a role in orchestrating the inflammatory response as well as cell proliferation in response to asbestos.
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Mice exposed to asbestos had higher total cell counts in BALF than air-exposed controls.
“As previously shown (19,20), asbestos-exposed mice exhibited increased total cell numbers in bronchoalveolar lavage fluid (BALF) compared to air-exposed mice.”
From Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica (2008) · cites this paper as [19]
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- Authors
- Haegens, A., Barrett, T. F., Gell, J., Shukla, A., MacPherson, M., Vacek, P., Poynter, M. E., Butnor, K. J., Janssen-Heininger, Y. M., Steele, C., & Mossman, B. T.
- Affiliations
- University of Vermont (US)
- Children's Hospital of Pittsburgh (US)
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-02-01
- Volume
- 178
- Issue
- 3
- Pages
- 1800-1808
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1640083684
- Cited by
- 48
- References
- 36
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 2 · 2015: 2 · 2014: 2 · 2012: 3
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL067004, P01 HL67004)
- National Institute of Environmental Health Sciences (T32ES007122)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- NF-κB, asbestos, chrysotile, airway epithelium, bronchiolar epithelium, IκBα, lung inflammation, pulmonary fibrosis, mucin production, eosinophils, epithelial cell proliferation, cytokines, bronchoalveolar lavage fluid, Ki-67
- MeSH terms
- NF-KappaB Inhibitor alpha, Animals, Asbestos, Bronchi, Bronchoalveolar Lavage Fluid, Cell Differentiation, Disease Models, Animal, Epithelial Cells, Inflammation, Mice, Transgenic, Mucins, Mutation, Cytokines, NF-kappa B, I-kappa B Proteins, Cell Proliferation, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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