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

F. Ricciardolo, Loredana Petecchia, Valentina Sorbello, Antonino Di Stefano, C. Usai, G. M. Massaglia, Isabella Gnemmi, B. Mognetti, Pieter S. Hiemstra, P. J. Sterk, Federica Sabatini

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)428-438
Number of pages11
JournalClinical and Experimental Allergy
Volume46
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

Keywords

  • Allergen
  • Asthma
  • Asthmatic fibroblasts
  • Bradykinin B2 receptor (B2R)
  • Nuclear factor-kappa B (NF-kB)

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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  • Cite this

    Ricciardolo, F., Petecchia, L., Sorbello, V., Di Stefano, A., Usai, C., Massaglia, G. M., Gnemmi, I., Mognetti, B., Hiemstra, P. S., Sterk, P. J., & Sabatini, F. (2016). Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: The role of NF-kB. Clinical and Experimental Allergy, 46(3), 428-438. https://doi.org/10.1111/cea.12676