Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 3259-3267 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 183 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2009 Sep 1 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Peroxisome proliferator-activated receptor γ agonist down-regulates IL-17 expression in a murine model of allergic airway inflammation. / Park, Seoung Ju; Lee, Kyung Sun; Kim, So Ri; Min, Kyung-Hoon; Choe, Yeong Hun; Moon, Hee; Chae, Han Jung; Yoo, Wan Hee; Lee, Yong Chul.
In: Journal of Immunology, Vol. 183, No. 5, 01.09.2009, p. 3259-3267.Research output: Contribution to journal › Article
}
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
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
VL - 183
SP - 3259
EP - 3267
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 5
ER -