title: Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: the role of NF-kB.
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
  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.
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano (Torino), Italy.
authors.forename: F L M
authors.initials: FL
authors.lastname: Ricciardolo
authors.affiliation: Institute of Biophysics, National Research Council of Italy (CNR), Genoa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Petecchia
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano (Torino), Italy.
authors.forename: V
authors.initials: V
authors.lastname: Sorbello
authors.affiliation: Pulmonary Division, Fondazione S. Maugeri, IRCCS, Veruno (Novara), Italy.
authors.forename: A
authors.initials: A
authors.lastname: Di Stefano
authors.affiliation: Institute of Biophysics, National Research Council of Italy (CNR), Genoa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Usai
authors.affiliation: Division of Respiratory Diseases, San Luigi Hospital, Orbassano (Torino), Italy.
authors.forename: G M
authors.initials: GM
authors.lastname: Massaglia
authors.affiliation: Pulmonary Division, Fondazione S. Maugeri, IRCCS, Veruno (Novara), Italy.
authors.forename: I
authors.initials: I
authors.lastname: Gnemmi
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano (Torino), Italy.
authors.forename: B
authors.initials: B
authors.lastname: Mognetti
authors.affiliation: Department of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: P S
authors.initials: PS
authors.lastname: Hiemstra
authors.affiliation: Department of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands.|Department of Respiratory Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
authors.affiliation: Laboratory of Stem cells and Cell therapy, Department of Experimental and Laboratory Medicine, G. Gaslini Institute, Genoa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Sabatini
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D001920:Bradykinin / Q000378:metabolism; D001980:Bronchi / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism*; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D012307:Risk Factors; D055815:Young Adult
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D000485:Allergens; D018793:Interleukin-13; D016328:NF-kappa B; D043782:Receptor, Bradykinin B2; D015847:Interleukin-4; D001920:Bradykinin
keywords: allergen; asthma; asthmatic fibroblasts; bradykinin B2 receptor (B2R); nuclear factor-kappa B (NF-kB)