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National Institute of Environmental Health Sciences

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Publication Detail

Title: Post-allergen challenge inhibition of poly(ADP-ribose) polymerase harbors therapeutic potential for treatment of allergic airway inflammation.

Authors: Naura, A S; Hans, C P; Zerfaoui, M; You, D; Cormier, S A; Oumouna, M; Boulares, A H

Published In Clin Exp Allergy, (2008 May)

Abstract: Identifying therapeutic drugs that block the release or effects of T-helper type 2 (Th2) cytokines after allergen exposure is an important goal for the treatment of allergic inflammatory diseases including asthma. We recently showed, using a murine model of allergic airway inflammation, that poly(ADP-ribose) polymerase (PARP) plays an important role in the pathogenesis of asthma-related lung inflammation. PARP inhibition, by single injection of a novel inhibitor, thieno[2,3-c]isoquinolin-5-one (TIQ-A), before ovalbumin (OVA) challenge, prevented airway eosinophilia in C57BL/6 mice with concomitant suppression of Th2 cytokine production and mucus secretion.To evaluate the efficacy of the drug when it is given after OVA challenge for its possible therapeutic potential.This study was conducted using a murine model of allergic airway inflammation.A single injection of TIQ-A (6 mg/kg) one or 6 h post-allergen challenge conferred similar reduction in OVA challenge-induced eosinophilia. More significantly, post-allergen challenge administration of the drug exerted even better suppression on the production of IL-4, IL-5, IL-13, and IgE and prevented airway hyperresponsiveness to inhaled-methacholine. The significant decrease in IL-13 was accompanied by a complete absence of airways mucus production indicating a potential protection against allergen-induced airway remodelling.The coincidence of the inflammation trigger and the time of drug administration appear to be important for the drug's more pronounced protection. The observed time window for efficacy, 1 or 6 h after allergen challenge may be of great clinical interest. These findings may provide a novel therapeutic strategy for the treatment of allergic airway inflammation, including asthma.

PubMed ID: 18261157 Exiting the NIEHS site

MeSH Terms: Allergens/administration & dosage*; Allergens/immunology; Animals; Cytokines/metabolism; Disease Models, Animal; Inflammation/drug therapy*; Isoquinolines/administration & dosage; Isoquinolines/therapeutic use*; Lung/drug effects; Lung/immunology; Lung/metabolism; Mice; Mice, Inbred C57BL; Mucus/drug effects; Mucus/secretion; Ovalbumin/administration & dosage; Ovalbumin/immunology; Poly(ADP-ribose) Polymerase Inhibitors*; Poly(ADP-ribose) Polymerases/metabolism; Respiratory Hypersensitivity/drug therapy*; Th2 Cells/drug effects; Th2 Cells/immunology; Thiophenes/administration & dosage; Thiophenes/therapeutic use*; Treatment Outcome

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