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

Fingerprint

Bradykinin B2 Receptors
NF-kappa B
Mucous Membrane
Allergens
Interleukin-13
Bradykinin
Interleukin-4
Asthma
Fibroblasts
Airway Remodeling
Biopsy
Bronchoscopy
Cytoplasmic and Nuclear Receptors
Fluorescence Microscopy
Confocal Microscopy
Cross-Sectional Studies
Western Blotting
Immunohistochemistry

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics : The role of NF-kB. / Ricciardolo, F.; Petecchia, Loredana; Sorbello, Valentina; Di Stefano, Antonino; Usai, C.; Massaglia, G. M.; Gnemmi, Isabella; Mognetti, B.; Hiemstra, Pieter S.; Sterk, P. J.; Sabatini, Federica.

In: Clinical and Experimental Allergy, Vol. 46, No. 3, 01.03.2016, p. 428-438.

Research output: Contribution to journalArticle

Ricciardolo, F, Petecchia, L, Sorbello, V, Di Stefano, A, Usai, C, Massaglia, GM, Gnemmi, I, Mognetti, B, Hiemstra, PS, Sterk, PJ & Sabatini, F 2016, 'Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: The role of NF-kB', Clinical and Experimental Allergy, vol. 46, no. 3, pp. 428-438. https://doi.org/10.1111/cea.12676
Ricciardolo F, Petecchia L, Sorbello V, Di Stefano A, Usai C, Massaglia GM et al. Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: The role of NF-kB. Clinical and Experimental Allergy. 2016 Mar 1;46(3):428-438. https://doi.org/10.1111/cea.12676
Ricciardolo, F. ; Petecchia, Loredana ; Sorbello, Valentina ; Di Stefano, Antonino ; Usai, C. ; Massaglia, G. M. ; Gnemmi, Isabella ; Mognetti, B. ; Hiemstra, Pieter S. ; Sterk, P. J. ; Sabatini, Federica. / Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics : The role of NF-kB. In: Clinical and Experimental Allergy. 2016 ; Vol. 46, No. 3. pp. 428-438.
@article{07d8f4294f1e469592c124f997e2d23a,
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 & 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.",
keywords = "Allergen, Asthma, Asthmatic fibroblasts, Bradykinin B2 receptor (B2R), Nuclear factor-kappa B (NF-kB)",
author = "F. Ricciardolo and Loredana Petecchia and Valentina Sorbello and {Di Stefano}, Antonino and C. Usai and Massaglia, {G. M.} and Isabella Gnemmi and B. Mognetti and Hiemstra, {Pieter S.} and Sterk, {P. J.} and Federica Sabatini",
year = "2016",
month = "3",
day = "1",
doi = "10.1111/cea.12676",
language = "English",
volume = "46",
pages = "428--438",
journal = "Clinical and Experimental Allergy",
issn = "0954-7894",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics

T2 - The role of NF-kB

AU - Ricciardolo, F.

AU - Petecchia, Loredana

AU - Sorbello, Valentina

AU - Di Stefano, Antonino

AU - Usai, C.

AU - Massaglia, G. M.

AU - Gnemmi, Isabella

AU - Mognetti, B.

AU - Hiemstra, Pieter S.

AU - Sterk, P. J.

AU - Sabatini, Federica

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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.

AB - 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.

KW - Allergen

KW - Asthma

KW - Asthmatic fibroblasts

KW - Bradykinin B2 receptor (B2R)

KW - Nuclear factor-kappa B (NF-kB)

UR - http://www.scopus.com/inward/record.url?scp=84959057053&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959057053&partnerID=8YFLogxK

U2 - 10.1111/cea.12676

DO - 10.1111/cea.12676

M3 - Article

VL - 46

SP - 428

EP - 438

JO - Clinical and Experimental Allergy

JF - Clinical and Experimental Allergy

SN - 0954-7894

IS - 3

ER -