Neurokinin-1 receptor activation induces reactive oxygen species and epithelial damage in allergic airway inflammation

J. Springer, D. A. Groneberg, Q. T. Dinh, D. Quarcoo, E. Hamelmann, R. C. Braun-Dullaeus, P. Geppetti, S. D. Anker, A. Fischer

Research output: Contribution to journalArticlepeer-review

Abstract

Background: An induction of reactive oxygen species (ROS) is characteristic for inflammation but the exact pathways have not been identified for allergic airway diseases so far. Objective: The aim of this study was to characterize the role of the tachykinin NK-1 receptor on ROS production during allergen challenge and subsequent inflammation and remodelling. Methods: Precision-cut lung slices of ovalbumin (OVA)-sensitized mice were cultivated and ROS-generation in response to OVA challenge (10 μg/mL) was examined by the 2′,7′-dichloroflourescein-diacetate method. Long-term ROS effects on epithelial proliferation were investigated by 5-bromo-2′-deoxyuridine incorporation (72 h). In vivo, the results were validated in OVA-sensitized animals which were treated intra-nasally with either placebo, the tachykinin neurokinin 1 (NK-1) receptor antagonist SR 140333 or the anti-oxidant N-acetylcystein (NAC) before allergen challenge. Inflammatory infiltration and remodelling were assessed 48 h after allergen challenge. Results: ROS generation was increased by 3.7-fold, which was inhibited by SR 140333. [Sar 9,Met11(O2)]-Substance P (5 nm) caused a tachykinin NK-1 receptor-dependent fourfold increase in ROS generation. Epithelial proliferation was decreased by 68% by incubation with [Sar 9,Met11(O2)]-SP over 72 h. In-vivo, treatment with SR 140333 and NAC reduced epithelial damage (91.4% and 76.8% vs. placebo, respectively, P

Original languageEnglish
Pages (from-to)1788-1797
Number of pages10
JournalClinical and Experimental Allergy
Volume37
Issue number12
DOIs
Publication statusPublished - Dec 2007

Keywords

  • Airway
  • Allergy
  • Asthma
  • Neurogenic inflammation
  • Precision-cut lung slices
  • Proliferation
  • ROS
  • Tachykinin NK-1 receptor

ASJC Scopus subject areas

  • Immunology

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