• Seoung Ju Park, Kyung Sun Lee, So Ri Kim, Kyung Hoon Min, Yeong Hun Choe, Hee Moon, Han Jung Chae, Wan Hee Yoo, and Yong Chul Lee.
• Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, South Korea.
• J. Immunol. 2009 Sep 1; 183 (5): 3259-67.

AbstractPeroxisome proliferator-activated receptor gamma (PPARgamma) 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 PPARgamma on IL-17 production in airway inflammatory diseases. In this study, we used a mouse model of asthma to evaluate the effect of two PPARgamma 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 PPARgamma 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-kappaB activity and that a NF-kappaB 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 PPARgamma in asthma is partly mediated by regulation of IL-17 expression via NF-kappaB pathway.

46 keywords...

hide…