Toll-like receptor-9 agonist inhibits airway inflammation, remodeling and hyperreactivity in mice exposed to chronic environmental tobacco smoke and allergen

Dae Jin Song, Myung Goo Min, Marina Miller, Jae Youn Cho, Hye Yung Yum, David H. Broide

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: As passive environmental tobacco smoke (ETS) exposure in nonsmokers can increase both asthma symptoms and the frequency of asthma exacerbations, we utilized a mouse model, in which ovalbumin (OVA) + ETS induce significantly increased levels of eosinophilic airway inflammation and remodeling compared to either stimulus alone, to determine whether a Toll-like receptor-9 (TLR-9) agonist could reduce levels of airway inflammation, airway remodeling and airway hyperreactivity (AHR). Methods: Mice treated with or without a TLR-9 agonist were sensitized to OVA and challenged with OVA + ETS for 1 month. AHR to methacholine was assessed in intubated and ventilated mice. Lung Th2 cytokines and TGF-β1 were measured by ELISA. Lungs were processed for histology and immunohistology to quantify eosinophils, mucus, peribronchial fibrosis and smooth muscle changes using image analysis. Results: Administration of a TLR-9 agonist to mice coexposed to chronic ETS and chronic OVA allergen significantly reduced levels of eosinophilic airway inflammation, mucus production, peribronchial fibrosis, the thickness of the peribronchial smooth muscle layer, and AHR. The reduced airway remodeling in mice treated with the TLR-9 agonist was associated with significantly reduced numbers of peribronchial MBP+ and peribronchial TGF-β1+ cells, and with significantly reduced levels of lung Th2 cytokines [interleukin-5 and interleukin-13] and TGF-β1. Conclusion: These studies demonstrate that TLR-9-based therapies inhibit airway inflammation, remodeling and AHR in mice coexposed to ETS and allergen who exhibit enhanced airway inflammation and remodeling.

Original languageEnglish
Pages (from-to)285-296
Number of pages12
JournalInternational Archives of Allergy and Immunology
Volume151
Issue number4
DOIs
Publication statusPublished - 2010 Mar 1

    Fingerprint

Keywords

  • Airway hyperreactivity
  • Airway inflammation
  • Airway remodeling
  • Eosinophils
  • Toll-like receptor-9

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this