| First Author | Tully JE | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 12 | Pages | 5811-21 |
| PubMed ID | 24227776 | Mgi Jnum | J:207128 |
| Mgi Id | MGI:5554493 | Doi | 10.4049/jimmunol.1301329 |
| Citation | Tully JE, et al. (2013) Epithelial NF-kappaB orchestrates house dust mite-induced airway inflammation, hyperresponsiveness, and fibrotic remodeling. J Immunol 191(12):5811-21 |
| abstractText | NF-kappaB activation within the epithelium has been implicated in the pathogenesis of asthma, yet the exact role of epithelial NF-kappaB in allergen-induced inflammation and airway remodeling remains unclear. In the current study, we used an intranasal house dust mite (HDM) extract exposure regimen time course in BALB/c mice to evaluate inflammation, NF-kappaB activation, airway hyperresponsiveness (AHR), and airway remodeling. We used CC10-IkappaBalphaSR transgenic mice to evaluate the functional importance of epithelial NF-kappaB in response to HDM. After a single exposure of HDM, mRNA expression of proinflammatory mediators was significantly elevated in lung tissue of wild-type (WT) mice, in association with increases in nuclear RelA and RelB, components of the classical and alternative NF-kappaB pathway, respectively, in the bronchiolar epithelium. In contrast, CC10-IkappaBalphaSR mice displayed marked decreases in nuclear RelA and RelB and mRNA expression of proinflammatory mediators compared with WT mice. After 15 challenges with HDM, WT mice exhibited increases in inflammation, AHR, mucus metaplasia, and peribronchiolar fibrosis. CC10-IkappaBalphaSR transgenic mice displayed marked decreases in neutrophilic infiltration, tissue damping, and elastance parameters, in association will less peribronchiolar fibrosis and decreases in nuclear RelB in lung tissue. However, central airway resistance and mucus metaplasia remained elevated in CC10-IkappaBalphaSR transgenic mice, in association with the continued presence of lymphocytes, and partial decreases in eosinophils and IL-13. The current study demonstrates that following airway exposure with an asthma-relevant allergen, activation of classical and alternative NF-kappaB pathways occurs within the airway epithelium and may coordinately contribute to allergic inflammation, AHR, and fibrotic airway remodeling. |
