Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: the role of NF‐kB. Issue 3 (March 2016)

• Record Type: Journal Article
• Authors: Ricciardolo, F. L. M.; Petecchia, L.; Sorbello, V.; Di Stefano, A.; Usai, C.; Massaglia, G. M.; Gnemmi, I.; Mognetti, B.; Hiemstra, P. S.; Sterk, P. J.; Sabatini, F.
• Is Part Of: Clinical & experimental allergy. Volume 46:Issue 3(2016:Mar.)
• Page Start: 428
• Page End: 438
• Publication Date: 2016-03
• Subjects: allergen -- asthma -- asthmatic fibroblasts -- bradykinin B2 receptor (B2R) -- nuclear factor‐kappa B (NF‐kB); Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.12676
• Languages: English
• ISSNs: 0954-7894

Abstract

Summary: Background: Bradykinin (BK) mediates acute allergic asthma and airway remodelling. Nuclear factor‐kappa B (NF‐kB) is potentially involved in BK B2 receptor (B2R) regulation. Objective: In this observational cross‐sectional study, B2R and NF‐kB expression was evaluated in bronchial biopsies from mild asthmatics (after diluent/allergen challenge) and healthy controls, examining the role of NF‐kB in B2R expression in primary human fibroblasts from normal and asthmatic subjects (HNBFb and HABFb). Methods: B2R and NF‐kB (total and nuclear) expression was analysed by immunohistochemistry in biopsies from 10 mild intermittent asthmatics (48 h after diluent/allergen challenge) and 10 controls undergoing bronchoscopy. B2R co‐localization in 5B5 + and αSMA + mesenchymal cells was studied by immunofluorescence/confocal microscopy, and B2R expression in HABFb/HNBFb incubated with interleukin (IL)‐4/IL‐13 with/without BK, and after NF‐kB inhibitor, by Western blotting. Results: Bronchial mucosa B2R and nuclear NF‐kB expression was higher in asthmatics after diluent (B2R only) and allergen challenge than in controls ( P < 0.05), while B2R and NF‐kB (total and nuclear) increased after allergen compared with after diluent ( P < 0.05). Allergen exposure increased B2R expression in 5B5 + and αSMA + cells. Constitutive B2R protein expression was higher in HABFb than in HNBFb ( P < 0.05) and increased in both cell types after IL‐13 or IL‐4/IL‐13 and BK treatment. This increase was suppressed by a NF‐kB inhibitor ( P < 0.05). Conclusions & Clinical Relevance: Bronchial B2R expression is constitutively elevated in allergic asthma and is further increased after allergen exposure together with NF‐kB expression. NF‐kB inhibitor blocked IL‐4/IL‐13‐induced increase in B2R expression in cultured fibroblasts, suggesting a role as potential anti‐asthma drug.