NF-kappa B activation in airways modulates allergic inflammation but not hyperresponsiveness.
Journal of immunology (Baltimore, Md. : 1950) 2004 Dec 1; 173(11):7003-9
Poynter M ME, Cloots R R, van Woerkom T T, Butnor K KJ, Vacek P P, Taatjes D DJ, Irvin C CG, Janssen-Heininger Y YM
Vermont Lung Center and the Department of Medicine, Division of Pulmonary and Critical Care, University of Vermont, Burlington, VT 05405, USA.
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.