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

As a ligand-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPAR-gamma) plays a crucial role in allergic inflammation. Recently, the nuclear factor kappa B (NF-kappa B) pathway and PAK1 have been indicated to be associated with allergic diseases. However, the effect of PPAR-gamma on NF-kappa B and PAK1 production in food allergies is not known. This study aims to 1) systematically validate that the activation of PPAR-gamma attenuates allergic reactions and 2) elucidate the mechanism by which PPAR-gamma 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-gamma and characterized by increased levels of IFN-gamma and decreased levels of IL-4, IL-5, and TNF-alpha. Our data showed that activated PPAR-gamma has the potential to alleviate food allergies by enhancing intestinal mucosal integrity and tight junctions. Moreover, we found that PPAR-gamma activation inhibited mast cell degranulation both in vivo and in vitro. Our in vitro findings also showed that the activated PPAR-gamma 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-gamma activation. Collectively, these results demonstrate that PPAR-gamma is an important regulator of mast cell degranulation and the Th2-type response, which sheds new light on the importance of PPAR-gamma in food allergies.

Automated summary

This study found that activating PPAR-gamma can alleviate clinical symptoms and immune reactions in food allergies. Activation of PPAR-gamma can mitigate food allergies by enhancing intestinal mucosal integrity and tight junctions, and inhibiting mast cell degranulation. Furthermore, PPAR-gamma activation can also inhibit PAK1 phosphorylation and p65 expression.