title: Peroxisome proliferator-activated receptor gamma agonist down-regulates IL-17 expression in a murine model of allergic airway inflammation.
abstract: Peroxisome 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.
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, South Korea.
authors.forename: Seoung Ju
authors.initials: SJ
authors.lastname: Park
authors.forename: Kyung Sun
authors.initials: KS
authors.lastname: Lee
authors.forename: So Ri
authors.initials: SR
authors.lastname: Kim
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Min
authors.forename: Yeong Hun
authors.initials: YH
authors.lastname: Choe
authors.forename: Hee
authors.initials: H
authors.lastname: Moon
authors.forename: Han Jung
authors.initials: HJ
authors.lastname: Chae
authors.forename: Wan Hee
authors.initials: WH
authors.lastname: Yoo
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D005260:Female; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000502:physiology; D020381:Interleukin-17 / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000502:physiology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism* / Q000627:therapeutic use; D000077205:Pioglitazone; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000276:immunology; D045162:Thiazolidinediones / Q000008:administration & dosage
chemical_list: D018836:Inflammation Mediators; D020381:Interleukin-17; D016328:NF-kappa B; D047495:PPAR gamma; D011994:Recombinant Proteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D010047:Ovalbumin; D000077205:Pioglitazone