Inhibition effect of PPAR-γ signaling on mast cell-mediated allergic inflammation through down-regulation of PAK1/ NF-κB activation

As a ligand-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPAR-γ) plays a crucial role in allergic inflammation. Recently, the nuclear factor kappa B (NF-κB) pathway and PAK1 have been indicated to be associated with allergic diseases. However, the effect of PPAR-γ on NF-κB and PAK1 production in food allergies is not known. This study aims to 1) systematically validate that the activation of PPAR-γ attenuates allergic reactions and 2) elucidate the mechanism by which PPAR-γ regulates mast cell degranulation. Brown Norway rats were separated into control, ovalbumin, ovalbumin + rosiglitazone, and ovalbumin + GW9662 groups. In vivo experiments demonstrated that rosiglitazone administration markedly inhibited the clinical symptoms and the serum levels of immunoglobulins E and G1. In addition, cytokine release was regulated by activated PPAR-γ and characterized by increased levels of IFN-γ and decreased levels of IL-4, IL-5, and TNF-α. Our data showed that activated PPAR-γ has the potential to alleviate food allergies by enhancing intestinal mucosal integrity and tight junctions. Moreover, we found that PPAR-γ activation inhibited mast cell degranulation both in vivo and in vitro. Our in vitro findings also showed that the activated PPAR-γ signal could inhibit PAK1 phosphorylation and the expression of p65. Furthermore, the interaction between p65 and p-PAK1 during ovalbumin treatment was attenuated after PPAR-γ activation. Collectively, these results demonstrate that PPAR-γ is an important regulator of mast cell degranulation and the Th2-type response, which sheds new light on the importance of PPAR-γ in food allergies.