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Glutathione S-transferase M1 modulates allergen-induced NF-κB activation in asthmatic airway epithelium.
MedLine Citation:
PMID:  25118837     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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: Post-allergen 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. This article is protected by copyright. All rights reserved.
Authors:
Vasiliy V Polosukhin; Igor V Polosukhin; Aimee Hoskins; Wei Han; Rasul Abdolrasulnia; Timothy S Blackwell; Ryszard Dworski
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-13
Journal Detail:
Title:  Allergy     Volume:  -     ISSN:  1398-9995     ISO Abbreviation:  Allergy     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804028     Medline TA:  Allergy     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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