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

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69 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

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ASJC Scopus subject areas

  • Immunology

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