NF-kappa B activation in airways modulates allergic inflammation but not hyperresponsiveness

• Published in: The Journal of immunology (1950) Vol. 173; no. 11; pp. 7003 - 7009
• Main Authors: Poynter, Matthew E, Cloots, Roy, van Woerkom, Tiest, Butnor, Kelly J, Vacek, Pamela, Taatjes, Douglas J, Irvin, Charles G, Janssen-Heininger, Yvonne M W
• Format: Journal Article
• Language: English
• Published: United States 01.12.2004
• Subjects: Allergens - administration & dosage; Allergens - immunology; Animals; Antibody Specificity - genetics; Bronchial Hyperreactivity - genetics; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - pathology; Chemokines - antagonists & inhibitors; Chemokines - biosynthesis; Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; I-kappa B Proteins - genetics; Immunoglobulin E - biosynthesis; Inflammation - genetics; Inflammation - immunology; Inflammation - prevention & control; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; Inflammation Mediators - physiology; Lung - immunology; Lung - metabolism; Lung - pathology; Mice; Mice, Inbred BALB C; Mice, Transgenic; Mucus - metabolism; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-kappa B - physiology; NF-KappaB Inhibitor alpha; Ovalbumin - administration & dosage; Ovalbumin - immunology; Respiratory Hypersensitivity - genetics; Respiratory Hypersensitivity - immunology; Respiratory Hypersensitivity - pathology; Respiratory Hypersensitivity - prevention & control; Respiratory Mucosa - immunology; Respiratory Mucosa - metabolism; Respiratory Mucosa - pathology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.11.7003

Airways display robust NF-kappaB activation and represent targets for anti-inflammatory asthma therapies, but the functional importance of NF-kappaB activation in airway epithelium remains enigmatic. Therefore, transgenic mice were created in which NF-kappaB activation is repressed specifically in airways (CC10-IkappaBalpha(SR) mice). In response to inhaled Ag, transgenic mice demonstrated significantly ameliorated inflammation, reduced levels of chemokines, T cell cytokines, mucus cell metaplasia, and circulating IgE compared with littermate controls. Despite these findings, Ag-driven airways hyperresponsiveness was not attenuated in CC10-IkappaBalpha(SR) mice. This study clearly demonstrates that airway epithelial NF-kappaB activation orchestrates Ag-induced inflammation and subsequent adaptive immune responses, but does not contribute to airways hyperresponsiveness, the cardinal feature that underlies asthma.