Lipocalin2 (lcn2) is Upregulated and May Serve as a Novel Protective Factor in Allergic Airway Disease

Abstract

RATIONALE: Allergen-induced bronchial asthma is a chronic airway disease that involves the interplay of various genes with environmental factors triggering numerous inflammatory pathways. We sought to identify novel common inflammatory mediators playing an important role in the pathogenesis of allergic airway disease independently of atopic susceptibility. METHODS: In a mouse model of allergic airway inflammation whole lung RNA expression was compared between mice with increased allergic receptiveness, (BALB/c) and mice with lower allergic susceptibility (C57/Bl6) by using microarray based RNA expression analysis. Results were confirmed by western blot analysis of mouse bronchoalveolar lavage fluid. The location of the target proteins was determined by immune-histological staining (IHC) of murine airway tissues. Functional relevance of the target was assessed using a blocking antibody directed against the LCN2. RESULTS: The expression of LCN2, a protein with yet an undefined role in the pathogenesis of allergic airway inflammation, was significantly increased in both strains after allergen sensitization and airway provocation on the RNA and protein level. LCN2 expression in lung tissue was localized to epithelial cells by IHC. Intranasal application of a blocking antibody against LCN2 resulted in increased eosinphilic airway inflammation, suggesting a protective role for LCN2 in allergic airway disease. CONCLUSIONS: These data suggest that LCN2 is a new mediator in allergic airway disease with a potential protective role. Due to its known role in mediating LPS-induced effects on immune cells, LCN2 possibly constitutes another molecule linking innate and adaptive immune responses in allergic airway disease.