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Airway epithelial NF-kappaB activation modulates asbestos-induced inflammation and mucin production in vivo.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2007 Feb 01; Vol. 178 (3), pp. 1800-8. - Publication Year :
- 2007
-
Abstract
- To investigate the role of bronchiolar epithelial NF-kappaB activity in the development of inflammation and fibrogenesis in a murine model of asbestos inhalation, we used transgenic (Tg) mice expressing an IkappaBalpha mutant (IkappaBalphasr) resistant to phosphorylation-induced degradation and targeted to bronchial epithelium using the CC10 promoter. Sham and chrysotile asbestos-exposed CC10-IkappaBalphasr 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-1beta were increased (p < or = 0.05) in bronchoalveolar lavage fluid (BALF) from asbestos-exposed mice, but to a lesser extent (p < or = 0.05) in Tg(+) vs Tg(-) mice. Asbestos also caused increases in IL-4, MIP-1beta, and MCP-1 in BALF that were more elevated (p < or = 0.05) in Tg(+) mice at 9 days. Differential cell counts revealed eosinophils in BALF that increased (p < or = 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 < or = 0.05) in Tg(+) vs Tg(-) mice. Our findings demonstrate that airway epithelial NF-kappaB activity plays a role in orchestrating the inflammatory response as well as cell proliferation in response to asbestos.
- Subjects :
- Animals
Bronchoalveolar Lavage Fluid chemistry
Bronchoalveolar Lavage Fluid cytology
Cell Differentiation
Cell Proliferation
Cytokines analysis
Cytokines biosynthesis
Disease Models, Animal
Epithelial Cells pathology
I-kappa B Proteins genetics
Mice
Mice, Transgenic
Mutation
NF-KappaB Inhibitor alpha
Asbestos adverse effects
Bronchi cytology
Epithelial Cells metabolism
Inflammation chemically induced
Mucins biosynthesis
NF-kappa B metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 178
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 17237430
- Full Text :
- https://doi.org/10.4049/jimmunol.178.3.1800