Peroxisome proliferator-activated receptor gamma agonist down-regulates IL-17 expression in a murine model of allergic airway inflammation.
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.
Park
Seoung Ju
SJ
Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, South Korea.
Lee
Kyung Sun
KS
Kim
So Ri
SR
Min
Kyung Hoon
KH
Choe
Yeong Hun
YH
Moon
Hee
H
Chae
Han Jung
HJ
Yoo
Wan Hee
WH
Lee
Yong Chul
YC
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
D018836:Inflammation Mediators; D020381:Interleukin-17; D016328:NF-kappa B; D047495:PPAR gamma; D011994:Recombinant Proteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D010047:Ovalbumin; D000077205:Pioglitazone