Glutathione S-transferase M1 modulates allergen-induced NF-κB activation in asthmatic airway epithelium

Allergy. 2014 Dec;69(12):1666-72. doi: 10.1111/all.12506. Epub 2014 Oct 1.


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-κB activation in bronchial epithelium in atopic asthmatics. We determined regulation of allergen-induced NF-κB 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-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 GSTM1+ compared to GSTM1null asthmatics. Airway eosinophilia was similar in GSTM1+ and GSTM1null asthmatics. Allergen-provoked NF-κB induction in bronchial epithelium was significantly greater in GSTM1+ compared to GSTM1null asthmatics. Activation of NF-κB 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-κB 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.

Keywords: GSTM1 polymorphism; NF-κB; airway epithelium; atopic asthma; neutrophilic airway inflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Allergens / immunology*
  • Animals
  • Asthma / diagnosis
  • Asthma / drug therapy
  • Asthma / immunology*
  • Asthma / metabolism*
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / metabolism
  • Enzyme Activation
  • Eosinophils / immunology
  • Eosinophils / pathology
  • Female
  • Genotype
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism*
  • Humans
  • Male
  • Middle Aged
  • NF-kappa B / metabolism*
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / pathology
  • Young Adult


  • Allergens
  • Cytokines
  • NF-kappa B
  • Glutathione Transferase
  • glutathione S-transferase M1