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)-κB within the bronchiolar epithelium and increased luciferase activity in lungs of mice containing a NF-κB-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-κB-dependent mediators that play a role in asthma.
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Supported by an NRSA Individual Postdoctoral Fellowship and a Senator Proctor Research Fund grant from the American Lung Association of Vermont and the Vermont Department of Health (to M.E.P.), by National Institutes of Health grant RO1 HL60014 and Public Health Service grants P20 RL15557 and PO1 HL67004 (to Y.J-H.), and by National Institutes of Health grant RO1 HL56638 and Public Health Service grants P20 RR15557 and P01 HL67004 (to C.G.I.).
