Glutathione S-transferase M1 modulates allergen-induced NF-[kappa]B activation in asthmatic airway epithelium

• Published in: Allergy (Copenhagen) Vol. 69; no. 12; p. 1666
• Main Authors: Polosukhin, V V, Polosukhin, I V, Hoskins, A, Han, W, Abdolrasulnia, R, Blackwell, T S, Dworski, R
• Format: Journal Article
• Language: English
• Published: Zurich Blackwell Publishing Ltd 01-12-2014
• Subjects: Allergies; Asthma; Enzymes; Polymorphism
• DOI: 10.1111/all.12506
• EISSN: 1398-9995
• ISSN: 0105-4538

Background Glutathione S-transferase M1 (GSTM1) 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 GSTM1 gene (GSTM1+) compared to GSTM1null asthmatics. We hypothesized that GSTM1 modulates NF-[kappa]B activation in bronchial epithelium in atopic asthmatics. We determined regulation of allergen-induced NF-[kappa]B activation in bronchial epithelium by GSTM1 in human atopic asthmatics in vivo. Methods Endobronchial biopsies and bronchoalveolar lavage fluid samples were collected from 13 GSTM1+ and 12 GSTM1null human atopic asthmatics at baseline and 24 h after segmental allergen challenge. A quantitative analysis of NF-[kappa]B activation in airway epithelium was accomplished using a polyclonal antibody against the phosphorylated p65 component of NF-[kappa]B. Elastase-positive neutrophils in the bronchial wall were quantified. Results Postallergen neutrophilia in airway subepithelium and epithelial lining fluid was greater in GSTM1+ compared to GSTM1null asthmatics. Airway eosinophilia was similar in GSTM1+ and GSTM1null asthmatics. Allergen-provoked NF-[kappa]B induction in bronchial epithelium was significantly greater in GSTM1+ compared to GSTM1null asthmatics. Activation of NF-[kappa]B activation in airway epithelial cells correlated with interleukin-8 concentrations and absolute neutrophil numbers in bronchoalveolar lavage fluid in GSTM1+ but not GSTM1null asthmatics. Conclusions Allergen-induced neutrophilic airway inflammation in GSTM1+ asthmatics is associated with NF-[kappa]B activation in airway epithelial cells in vivo. These novel data provide a potential mechanism of the genomic link between GSTM1 polymorphism and airway neutrophilia in atopic asthma.