Rapid activation of nuclear factor-kappaB in airway epithelium in a murine model of allergic airway inflammation.
Bronchiolar epithelium is postulated to play a critical role in the orchestration of responses to inhaled allergens, and may contribute to the pathogenesis of asthma. Using a murine model of allergic airway inflammation and hyperresponsiveness, we demonstrate in mice sensitized with ovalbumin (OVA) that following a single challenge with nebulized OVA, a rapid and protracted activation of inhibitor of kappa B kinase (IKK) occurred in lung tissue. IKK activation was followed by nuclear localization of nuclear factor (NF)-kappaB within the bronchiolar epithelium and increased luciferase activity in lungs of mice containing a NF-kappaB-dependent reporter gene. Challenge of sensitized mice with OVA also induced mRNA expression of the chemokines, macrophage inflammatory protein-2 (MIP-2) and eotaxin in lung tissue, which corresponded temporally with the observed influx of neutrophils and eosinophils, respectively, into the airspaces. Using laser capture microdissection and quantitative polymerase chain reaction, we demonstrated that MIP-2 and eotaxin were predominantly expressed in bronchiolar epithelium, in contrast to distal regions of the lungs, which expressed lower or undetectable levels of these mRNAs. These studies strengthen the potential importance of the bronchiolar epithelial cell as a source of production of NF-kappaB-dependent mediators that play a role in asthma.
Poynter
Matthew E
ME
Vermont Lung Center and Department of Pathology, University of Vermont, Burlington 05405, USA.
Irvin
Charles G
CG
Janssen-Heininger
Yvonne M W
YM
D000485:Allergens / Q000276:immunology; D000818:Animals; D001980:Bronchi / Q000276:immunology / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000378:metabolism; D001991:Bronchitis / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics; D006967:Hypersensitivity / Q000378:metabolism*; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
D000485:Allergens; D018925:Chemokines; D016328:NF-kappa B