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Glutathione S-transferase P1 Ile105Val polymorphism modulates allergen-induced airway inflammation in human atopic asthmatics in vivo.

AbstractBACKGROUND:
Glutathione S-transferase P1 is a Phase II cytoprotective and detoxifying enzyme that is widely expressed in human airways. The glutathione S-transferase P1 Ile105Val polymorphism has been linked with atopic disorders and asthma. Yet, little remains known about the regulation of allergic inflammation by glutathione S-transferase P1 in human asthmatics.
OBJECTIVE:
To establish the effect of the glutathione S-transferase P1 Ile105Val polymorphism on allergen-induced airway inflammation and oxidant stress, and non-specific bronchial hyperresponsiveness to methacholine and reactivity to specific allergen in mild human atopic asthmatics in vivo.
METHODS:
Five Val(105)/Val(105) , twelve Val(105)/Ile(105) and twenty Ile(105)/Ile(105) mild atopic asthmatics underwent methacholine challenge, inhaled allergen challenge and endobronchial allergen provocation through a bronchoscope. A panel of inflammatory cytokines and chemokines, F2 -isoprostanes and isofuranes, markers of oxidative stress, thromboxane B2 and immunoglobulin E were measured in bronchoalveolar lavage fluid at baseline and 24 h after allergen instillation.
RESULTS:
Asthmatics with glutathione S-transferase P1 Val(105)/Val(105) compared with asthmatics with the glutathione S-transferase P1 Val(105)/Ile(105) and Ile(105)/Ile(105) had greater generation of acute phase cytokines (TNF-α, IL-6, CXCL8), IL-12, CCL11, thromboxane B2 and immunoglobulin E at 24 h after local allergen challenge. The GSTP1 genotype had no effect on airway hyperresponsiveness to methacholine and the reactivity to specific allergen.
CONCLUSION:
The glutathione S-transferase P1 Ile105Val polymorphism markedly modifies allergen-provoked airway inflammation in atopic asthmatics in vivo. Modulation of the biochemical milieu in response to allergen provides a mechanistic explanation for regulatory effects of glutathione S-transferase P1 polymorphism on airway pathophysiology, and may guide improvement of future therapeutic methods in human atopic asthmatics. These findings must me confirmed in a larger study population of asthmatics with various ethnicities.
AuthorsA Hoskins, P Wu, S Reiss, R Dworski
JournalClinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 43 Issue 5 Pg. 527-34 (May 2013) ISSN: 1365-2222 [Electronic] England
PMID23600543 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright© 2013 Blackwell Publishing Ltd.
Chemical References
  • Allergens
  • Inflammation Mediators
  • Immunoglobulin E
  • Glutathione S-Transferase pi
Topics
  • Adult
  • Allergens (immunology)
  • Asthma (genetics, immunology, metabolism)
  • Bronchial Hyperreactivity (immunology, metabolism)
  • Bronchoalveolar Lavage Fluid (cytology, immunology)
  • Female
  • Glutathione S-Transferase pi (genetics)
  • Humans
  • Hypersensitivity, Immediate (genetics, immunology, metabolism)
  • Immunoglobulin E (immunology)
  • Inflammation Mediators (immunology, metabolism)
  • Male
  • Middle Aged
  • Oxidative Stress
  • Polymorphism, Genetic
  • Young Adult

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