Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: the role of NF-kB

• Published in: Clinical and experimental allergy Vol. 46; no. 3; pp. 428 - 438
• Main 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.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-03-2016; Wiley Subscription Services, Inc
• Subjects: Actins - genetics; Actins - metabolism; Adult; allergen; Allergens - immunology; asthma; Asthma - diagnosis; Asthma - genetics; Asthma - immunology; Asthma - metabolism; asthmatic fibroblasts; Bradykinin - metabolism; bradykinin B2 receptor (B2R); Bronchi - immunology; Bronchi - metabolism; Bronchi - pathology; Cross-Sectional Studies; Female; Fibroblasts - metabolism; Gene Expression; Humans; Immunohistochemistry; Interleukin-13 - metabolism; Interleukin-4 - metabolism; Male; NF-kappa B - metabolism; nuclear factor-kappa B (NF-kB); Receptor, Bradykinin B2 - genetics; Receptor, Bradykinin B2 - metabolism; Respiratory Function Tests; Respiratory Mucosa - immunology; Respiratory Mucosa - metabolism; Respiratory Mucosa - pathology; Risk Factors; Young Adult; allergen; asthmatic fibroblasts; asthma; nuclear factor-kappa B (NF-kB); bradykinin B2 receptor (B2R)
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/cea.12676

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.