TY - JOUR
T1 - Peroxisome proliferator-activated receptor γ agonist down-regulates IL-17 expression in a murine model of allergic airway inflammation
AU - Park, Seoung Ju
AU - Lee, Kyung Sun
AU - Kim, So Ri
AU - Min, Kyung Hoon
AU - Choe, Yeong Hun
AU - Moon, Hee
AU - Chae, Han Jung
AU - Yoo, Wan Hee
AU - Lee, Yong Chul
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/9/1
Y1 - 2009/9/1
N2 - Peroxisome proliferator-activated receptor γ(PPARγ) plays a critical role in the control of airway inflammation. Recently, IL-17 has been found to be implicated in many immune and inflammatory responses, including airway inflammation. However, no data are available concerning the effect of PPARγ on IL-17 production in airway inflammatory diseases. In this study, we used a mouse model of asthma to evaluate the effect of two PPARγ agonists, rosiglitazone or pioglitazone, on IL-17 expression in allergic airway disease. After OVA inhalation, mice developed the typical pathophysiological features of asthma, and the expression of IL-17 protein and mRNA in the lungs was increased. Administration of rosiglitazone or pioglitazone reduced the pathophysiological features of asthma and decreased the increased IL-17 protein and mRNA expression after OVA inhalation. In addition, the attenuating effect of PPARγ agonist on allergic airway inflammation and bronchial hyperresponsiveness is abrogated by coadministration of rIL-17. This study also showed that the inhibition of IL-17 activity with anti-IL-17 Ab remarkably reduced the increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, and the increased levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid and OVA-specific IgE in serum. In addition, we found that administration of rosiglitazone or pioglitazone decreased the increased NF-κB activity and that a NF-κB inhibitor, BAY 11-7085, substantially reduced the increased IL-17 protein levels in the lung tissues after OVA inhalation. These findings suggest that the therapeutic effect of PPARγ in asthma is partly mediated by regulation of IL-17 expression via NF-κB pathway.
AB - Peroxisome proliferator-activated receptor γ(PPARγ) plays a critical role in the control of airway inflammation. Recently, IL-17 has been found to be implicated in many immune and inflammatory responses, including airway inflammation. However, no data are available concerning the effect of PPARγ on IL-17 production in airway inflammatory diseases. In this study, we used a mouse model of asthma to evaluate the effect of two PPARγ agonists, rosiglitazone or pioglitazone, on IL-17 expression in allergic airway disease. After OVA inhalation, mice developed the typical pathophysiological features of asthma, and the expression of IL-17 protein and mRNA in the lungs was increased. Administration of rosiglitazone or pioglitazone reduced the pathophysiological features of asthma and decreased the increased IL-17 protein and mRNA expression after OVA inhalation. In addition, the attenuating effect of PPARγ agonist on allergic airway inflammation and bronchial hyperresponsiveness is abrogated by coadministration of rIL-17. This study also showed that the inhibition of IL-17 activity with anti-IL-17 Ab remarkably reduced the increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, and the increased levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid and OVA-specific IgE in serum. In addition, we found that administration of rosiglitazone or pioglitazone decreased the increased NF-κB activity and that a NF-κB inhibitor, BAY 11-7085, substantially reduced the increased IL-17 protein levels in the lung tissues after OVA inhalation. These findings suggest that the therapeutic effect of PPARγ in asthma is partly mediated by regulation of IL-17 expression via NF-κB pathway.
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U2 - 10.4049/jimmunol.0900231
DO - 10.4049/jimmunol.0900231
M3 - Article
C2 - 19641141
AN - SCOPUS:70349249624
VL - 183
SP - 3259
EP - 3267
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 5
ER -