NF-kappa B activation in airways modulates allergic inflammation but not hyperresponsiveness.
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.
Poynter
Matthew E
ME
Vermont Lung Center and the Department of Medicine, Division of Pulmonary and Critical Care, University of Vermont, Burlington, VT 05405, USA.
Cloots
Roy
R
van Woerkom
Tiest
T
Butnor
Kelly J
KJ
Vacek
Pamela
P
Taatjes
Douglas J
DJ
Irvin
Charles G
CG
Janssen-Heininger
Yvonne M W
YM
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000918:Antibody Specificity / Q000235:genetics; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020672:I-kappa B Proteins / Q000235:genetics; D007073:Immunoglobulin E / Q000096:biosynthesis; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009093:Mucus / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D018925:Chemokines; D016207:Cytokines; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D007073:Immunoglobulin E; D010047:Ovalbumin