Modulation of airway remodeling and airway inflammation by peroxisome proliferator-activated receptor γ in a murine model of toluene diisocyanate-induced asthma

Kyung Sun Lee, Seoung Ju Park, So Ri Kim, Kyung Hoon Min, Sun M.I. Jin, Hern Ku Lee, Yong Chul Lee

    Research output: Contribution to journalArticlepeer-review

    64 Citations (Scopus)

    Abstract

    Toluene diisocyanate (TDI) is a leading cause of occupational asthma. Although considerable controversy remains regarding its pathogenesis, TDI-induced asthma is an inflammatory disease of the airways characterized by airway remodeling. Peroxisome proliferator-activated receptor γ (PPARγ) has been shown to play a critical role in the control of airway inflammatory responses. However, no data are available on the role of PPARγ in TDI-indiiced asthma. We have used a mouse model for TDI-induced asthma to determine the effect of PPARγ agonist, rosiglitazone, or pioglitazone, and PPARγ on TDI-induced bronchial inflammation and airway remodeling. This study with the TDI-induced model of asthma revealed the following typical pathophysiological features: increased nembers of inflammatory cells of the airways, airway hyperresponsiveness, increased levels of Th2 cytokines (IL-4, IL-5, and IL-13), adhesion molecules (ICAM-1 and VCAM-1), chemokines (RANTES and eotaxin), TGF-β1, and NF-κB in nuclear protein extracts. In addition, the mice exposed to TDI developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer, subepithelial collagen deposition, and increased airway mucus production. Administration of PPARγ agonists or adenovirus carrying PPARγ2 cDNA reduced the pathophysiological symptoms of asthma and decreased the increased levels of Th2 cytokines, adhesion molecules, chemokines, TGF-β1, and NF-κB in nuclear protein extracts after TDI inhalation. In addition, inhibition of NF-κB activation decreased the increased levels of Th2 cytokines, adhesion molecules, chemokines, and TGF-β1 after TDI inhalation. These findings demonstrate a protective role of PPARγ in the pathogenesis of the TDI-induced asthma phenotype.

    Original languageEnglish
    Pages (from-to)5248-5257
    Number of pages10
    JournalJournal of Immunology
    Volume177
    Issue number8
    DOIs
    Publication statusPublished - 2006 Oct 15

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Fingerprint

    Dive into the research topics of 'Modulation of airway remodeling and airway inflammation by peroxisome proliferator-activated receptor γ in a murine model of toluene diisocyanate-induced asthma'. Together they form a unique fingerprint.

    Cite this