title: Peroxisome proliferator-activated receptor-gamma agonist induces regulatory T cells in a murine model of allergic rhinitis.
abstract: OBJECTIVE
  To evaluate the effects of peroxisome proliferator-activated receptor (PPAR)-γ agonist on the induction of regulatory T cells (Tregs) in a murine model of allergic rhinitis.
  
  
  METHODS
  Randomized controlled trial.
  
  
  METHODS
  Animal study.
  
  
  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-γ agonist pioglitazone (30 mg/kg/d) or pioglitazone plus PPAR-γ 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-γ 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-γ agonist on Foxp3 mRNA expression and Tregs induction were abrogated by administration of GW9662.
  
  
  CONCLUSIONS
  PPAR-γ agonist attenuates upper airway allergic inflammation in a PPAR-γ-dependent fashion, and the beneficial effects of pioglitazone in airway allergic inflammation may be mediated by induction of Tregs.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Wang
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Zhu
authors.forename: Bingwei
authors.initials: B
authors.lastname: Zhu
authors.forename: Zhaoxin
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D050990:GATA3 Transcription Factor / Q000032:analysis; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D017817:Nasal Lavage Fluid / Q000737:chemistry / Q000166:cytology; D009297:Nasal Mucosa / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000276:immunology; D000077205:Pioglitazone; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D020825:T-Box Domain Proteins / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D045162:Thiazolidinediones / Q000494:pharmacology*; D000098815:T-bet Transcription Factor
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D015848:Interleukin-5; D047495:PPAR gamma; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D045162:Thiazolidinediones; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin; D000077205:Pioglitazone