The Novel PPAR alpha/gamma Dual Agonist MHY 966 Modulates UVB-Induced Skin Inflammation by Inhibiting NF-kappa B Activity

Abstract

Ultraviolet B (UVB; 290 similar to 320nm) irradiation-induced lipid peroxidation induces inflammatory responses that lead to skin wrinkle formation and epidermal thickening. Peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual agonists have the potential to be used as anti-wrinkle agents because they inhibit inflammatory response and lipid peroxidation. In this study, we evaluated the function of 2-bromo-4-(5-chloro-benzo[d]thiazol-2-yl) phenol (MHY 966), a novel synthetic PPAR alpha/gamma dual agonist, and investigated its anti-inflammatory and anti-lipid peroxidation effects. The action of MHY 966 as a PPAR alpha/gamma dual agonist was also determined in vitro by reporter gene assay. Additionally, 8-week-old melanin-possessing hairless mice 2 (HRM2) were exposed to 150 mJ/cm(2) UVB every other day for 17 days and MHY 966 was simultaneously pre-treated every day for 17 days to investigate the molecular mechanisms involved. MHY 966 was found to stimulate the transcriptional activities of both PPAR alpha and gamma. In HRM2 mice, we found that the skins of mice exposed to UVB showed significantly increased pro-inflammatory mediator levels (NF-kappa B, iNOS, and COX-2) and increased lipid peroxidation, whereas MHY 966 co-treatment down-regulated these effects of UVB by activating PPAR alpha and gamma. Thus, the present study shows that MHY 966 exhibits beneficial effects on inflammatory responses and lipid peroxidation by simultaneously activating PPAR alpha and gamma. The major finding of this study is that MHY 966 demonstrates potential as an agent against wrinkle formation associated with chronic UVB exposure.