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

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.

Peroxisome Proliferator-activated Receptor γ Negatively Regulates IFN-β Production in Toll-like Receptor (TLR) 3- and TLR4-stimulated Macrophages by Preventing Interferon Regulatory Factor 3 Binding to the IFN-β Promoter

“…PPAR-␥ has been reported to regulate the expression of macrophage colonystimulating factor in alveolar macrophages (18). PPAR-␥ agonist has been shown to down-regulate IL-17 expression in a murine model of allergic airway inflammation (19). PPAR-␥ is expressed in both murine CD4 and CD8 cells, and PPAR-␥ ligands directly decrease IFN-␥ expression in T cells (20).…”

The PPARγ agonist, rosiglitazone, attenuates airway inflammation and remodeling via heme oxygenase-1 in murine model of asthma

“…Then in the following 8 weeks, OVA (15 μg) was administered intranasally 3 days per week. For rosiglitazone treatment, rosiglitazone (GSK, 5 mg/kg) was administered orally 6 h prior to every OVA intranasal challenge [14] . For ZnPP treatment, ZnPP (SigmaAldrich, 10 mg/kg, dissolved in 5 mmol/L NaOH, pH=7.4) was administered intraperitoneally accompanied with every rosiglitazone treatment.…”

15d-PGJ2 modulates acute immune responses to Trypanosoma cruzi infection

“…As a consequence of the important roles, PPARs play in controlling metabolic homeostasis and inflammatory processes, they are often the therapeutic molecular targets for metabolic diseases such as diabetes (Chinetti et al 2000) and in the treatment of inflammatory disorders (Napimoga et al 2008, Hassumi et al 2009, Klotz et al 2009, Park et al 2009). In the present paper, we have investigated the effects of the 15d-PGJ 2 , an agonist of PPAR-γ, on disease outcome and immune function in T. cruzi-infected C57BL/6 mice.…”