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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0900231v1 183/5/3259    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Park, S. J. Articles by Lee, Y. C. PubMed PubMed Citation Articles by Park, S. J. Articles by Lee, Y. C.

Peroxisome Proliferator-Activated Receptor Agonist Down-Regulates IL-17 Expression in a Murine Model of Allergic Airway Inflammation¹

Seoung Ju Park^2,*,, Kyung Sun Lee^2,*,, So Ri Kim^*,, Kyung Hoon Min^*,, Yeong Hun Choe^*,, Hee Moon^*,, Han Jung Chae^,, Wan Hee Yoo^*, and Yong Chul Lee^3,*,

^* Department of Internal Medicine, Research Center for Pulmonary Disorders, and Department of Pharmacology, Chonbuk National University Medical School, Jeonju, South Korea

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

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A084144).

² These authors contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Yong Chul Lee, Department of Internal Medicine, Chonbuk National University Medical School, San 2-20 Geumam-dong, Deokjin-gu, Jeonju, Jeonbuk 561-180, South Korea. E-mail address: leeyc{at}chonbuk.ac.kr

⁴ Abbreviations used in this paper: BALF, bronchoalveolar lavage fluid; BAL, bronchoalveolar lavage; PAS, periodic acid-Schiff; PPAR, peroxisome proliferator-activated receptor; Rrs, respiratory system resistance.