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Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: the role of NF ‐ kB
Author(s) -
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.
Publication year - 2016
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12676
Subject(s) - bradykinin , receptor , chemistry , asthma , immunology , medicine
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 ( HNBF b and HABF b). 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 α SMA + mesenchymal cells was studied by immunofluorescence/confocal microscopy, and B2R expression in HABF b/ HNBF b 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 α SMA + cells. Constitutive B2R protein expression was higher in HABF b than in HNBF b ( 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.