Peroxisome proliferator-activated receptor-gamma agonist induces regulatory T cells in a murine model of allergic rhinitis.

摘要

OBJECTIVE: To evaluate the effects of peroxisome proliferator-activated receptor (PPAR)-gamma agonist on the induction of regulatory T cells (Tregs) in a murine model of allergic rhinitis. STUDY DESIGN: Randomized controlled trial. SETTING: Animal study. SUBJECTS AND METHODS: BALB/c mice that received ovalbumin sensitization and challenge served as the ovalbumin group (n = 6). Two separate groups of 6 mice received intragastric administration with PPAR-gamma agonist pioglitazone (30 mg/kg/d) or pioglitazone plus PPAR-gamma antagonist GW9662 (0.5 mg/d) before each ovalbumin challenge. The control group (n = 6) was treated with drug vehicle alone. Various allergic responses were assessed. Real-time polymerase chain reaction was performed to investigate the mRNA expression of forkhead box P3 (Foxp3), T-bet, and GATA-3. Flow cytometry was used to determine the percentage of Tregs. RESULTS: Mice developed typical pathophysiological allergic rhinitis features after the ovalbumin challenge. The frequencies of sneezing and scratching were significantly decreased by pioglitazone treatment (P < .0001). Eosinophils infiltration and the levels of interleukin-5 and interferon-gamma in nasal cavity lavage fluid and sera immunoglobulin E were also markedly decreased by pioglitazone (P < .001). The expression of Foxp3 mRNA and the population of Tregs were significantly increased by pioglitazone (P < .05). Cotreatment with GW9662 reversed the anti-inflammatory effects of pioglitazone. The effects of PPAR-gamma agonist on Foxp3 mRNA expression and Tregs induction were abrogated by administration of GW9662. CONCLUSION: PPAR-gamma agonist attenuates upper airway allergic inflammation in a PPAR-gamma-dependent fashion, and the beneficial effects of pioglitazone in airway allergic inflammation may be mediated by induction of Tregs.