Peroxisome proliferator-activated receptor γ agonist down-regulates IL-17 expression in a murine model of allergic airway inflammation

Seoung Ju Park, Kyung Sun Lee, So Ri Kim, Kyung Hoon Min, Yeong Hun Choe, Hee Moon, Han Jung Chae, Wan Hee Yoo, Yong Chul Lee

Research output: Contribution to journalArticle

71 Citations (Scopus)

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 languageEnglish
Pages (from-to)3259-3267
Number of pages9
JournalJournal of Immunology
Volume183
Issue number5
DOIs
Publication statusPublished - 2009 Sep 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Park, S. J., Lee, K. S., Kim, S. R., Min, K. H., Choe, Y. H., Moon, H., Chae, H. J., Yoo, W. H., & Lee, Y. C. (2009). Peroxisome proliferator-activated receptor γ agonist down-regulates IL-17 expression in a murine model of allergic airway inflammation. Journal of Immunology, 183(5), 3259-3267. https://doi.org/10.4049/jimmunol.0900231