Antiallergic Function of KR62980, a Peroxisome Proliferator-Activated Receptor-gamma Agonist, in a Mouse Allergic Rhinitis Model

ABSTRACT

PURPOSE: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) has been shown to play an important role in the control of inflammatory responses acting on macrophages, mast cells, T cells and eosinophils. A novel PPAR-gamma ligand, KR62980 have been recently focused on due to the lower undesirable effects than other PPAR-gamma ligands such as rosiglitazone and pioglitazone. The present study was aimed to investigate the effects of KR62980 on nasal symptoms and immunopathological profiles in allergic nasal mucosa in murine allergic rhinitis model. METHODS: BALB/c mice were sensitized and challenged intranasally with ovalbumin (OVA). KR62980 was administered intraperitoneally or orally 3 hours before each intranasal OVA challenge. RESULTS: Administration of KR62980 significantly decreased the number of nasal rubbing, nasal sneezing, ova-specific IgE and total IgE in serum, secretion of Interleukin (IL)-4, IL-5, and IL-17 from the spleen and eosinophilic infiltration in the nasal mucosa. KR62980 decreased the expression of IL-4, IL-5 and IL-10 mRNAs in the nasal mucosal tissue, while, it elevated the level of IL-10 and IFN-gamma in splenocyte culture. KR62980 seemed to decrease IL-17 level in local and systemic level even though it did not reach to statistical significance. The anti-inflammatory effect was more definite when the KR62980 was administered intraorally than intraperitoneally. CONCLUSIONS: A novel PPAR-gamma ligand, KR62980 can attenuate OVA-induced allergic inflammation in mice mainly through modulation of Th2 cytokines. This finding suggests that PPAR-gamma might have a role in the treatment of allergic rhinitis.