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Glutathione S ‐transferase M1 modulates allergen‐induced NF ‐κ B activation in asthmatic airway epithelium
Author(s) -
Polosukhin V. V.,
Polosukhin I. V.,
Hoskins A.,
Han W.,
Abdolrasulnia R.,
Blackwell T. S.,
Dworski R.
Publication year - 2014
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12506
Subject(s) - neutrophilia , bronchoalveolar lavage , immunology , medicine , respiratory epithelium , eosinophilia , allergen , bronchoconstriction , eosinophil , respiratory tract , epithelium , asthma , allergy , pathology , lung , respiratory system
Background Glutathione S‐transferase M1 ( GSTM 1) is a phase II enzyme and regulator of inflammatory signaling in airway epithelial cells. We have found upregulation of neutrophilic airway inflammation in atopic asthmatics expressing GSTM 1 gene ( GSTM 1+) compared to GSTM 1 null asthmatics. We hypothesized that GSTM 1 modulates NF ‐κB activation in bronchial epithelium in atopic asthmatics. We determined regulation of allergen‐induced NF ‐κB activation in bronchial epithelium by GSTM 1 in human atopic asthmatics in vivo . Methods Endobronchial biopsies and bronchoalveolar lavage fluid samples were collected from 13 GSTM 1+ and 12 GSTM 1 null human atopic asthmatics at baseline and 24 h after segmental allergen challenge. A quantitative analysis of NF ‐κB activation in airway epithelium was accomplished using a polyclonal antibody against the phosphorylated p65 component of NF ‐κB. Elastase‐positive neutrophils in the bronchial wall were quantified. Results Postallergen neutrophilia in airway subepithelium and epithelial lining fluid was greater in GSTM 1+ compared to GSTM 1 null asthmatics. Airway eosinophilia was similar in GSTM 1+ and GSTM 1 null asthmatics. Allergen‐provoked NF ‐κB induction in bronchial epithelium was significantly greater in GSTM 1+ compared to GSTM 1 null asthmatics. Activation of NF ‐κB activation in airway epithelial cells correlated with interleukin‐8 concentrations and absolute neutrophil numbers in bronchoalveolar lavage fluid in GSTM 1+ but not GSTM 1 null asthmatics. Conclusions Allergen‐induced neutrophilic airway inflammation in GSTM 1+ asthmatics is associated with NF ‐κB activation in airway epithelial cells in vivo . These novel data provide a potential mechanism of the genomic link between GSTM 1 polymorphism and airway neutrophilia in atopic asthma.