TY - JOUR
T1 - Modulation of airway remodeling and airway inflammation by peroxisome proliferator-activated receptor γ in a murine model of toluene diisocyanate-induced asthma
AU - Lee, Kyung Sun
AU - Park, Seoung Ju
AU - Kim, So Ri
AU - Min, Kyung Hoon
AU - Jin, Sun M.I.
AU - Lee, Hern Ku
AU - Lee, Yong Chul
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2006/10/15
Y1 - 2006/10/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.177.8.5248
DO - 10.4049/jimmunol.177.8.5248
M3 - Article
C2 - 17015710
AN - SCOPUS:33749517887
VL - 177
SP - 5248
EP - 5257
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 8
ER -