Preventive effects of ß-thujaplicin against UVB-induced MMP-1 and MMP-3 mRNA expressions in skin fibroblasts.

ABSTRACT

Solar UV radiation damages human skin by affecting skin tone and resiliency and leads to premature aging (photoaging). The skin damage is caused by the activation of the AP-1 transcription factor, which increases matrix metalloproteinase (MMP) expression and collagen degradation. An increase of interleukin (IL)-6 is also correlated with the activation of MMP-1 expression. ß-thujaplicin has shown both acaricidal and antimicrobial activities. Also, ß-thujaplicin has been shown to be protective against apoptosis due to the oxidative effects of UV irradiation. However, the effect of ß-thujaplicin on UVB-induced MMPs had not been investigated. In this study, after UVB exposure, MMP-1 and IL-6 production in human skin fibroblasts was examined in the presence of ß-thujaplicin, vitamin C, and vitamin E. The expression of MMP-1, MMP-3, tissue inhibitor of metalloproteinase (TIMP-1, TIMP-3) and procollagen mRNA was also investigated. Results showed that UVB-induced MMP-1 production was suppressed by the ß-thujaplicin treatment in a dose-dependent manner, but not by vitamin C and vitamin E. ß-thujaplicin also prevented the up-regulation of MMP-1 and MMP-3 mRNA. Moreover, the UVB-suppressed procollagen gene expression was restored to normal by ß-thujaplicin. Neither UVB nor ß-thujaplicin affected the mRNA expression of TIMP-1 and TIMP-3. The IL-6 production induced by UVB was lower in ß-thujaplicin treated fibroblasts than in the controls. In conclusion, this study shows the capability of ß-thujaplicin in preventing MMP-1 production due to UVB irradiation via inhibition of MMP gene expression. Importantly, the UVB-suppressed procollagen gene expression can be restored to normal by ß-thujaplicin. These findings indicate that ß-thujaplicin is a promising and potent agent to inhibit UVB-induced MMP-1 and MMP-3 gene expression in skin fibroblasts.