Influence of flavonoids and vitamins on the MMP- and TIMP-expression of human dermal fibroblasts after UVA irradiation.

Abstract

UV irradiation leads to distinct changes in skin connective tissue by degradation of collagen, for example. Many of these alterations in the extracellular matrix are mediated by MMPs (matrix metalloproteinases) with reduced content of their antagonist TIMPs (tissue inhibitors of metalloproteinases). Potential candidates to reduce MMP activity in the skin after solar stimulation were examined. The influence of vitamin C, vitamin E and the flavonoids AGR (alpha-glucosylrutin) and 8-prenylnaringenine on the MMP and TIMP expression was investigated. Human dermal fibroblasts were incubated with these additives and irradiated with UVA [10 J cm(-2)]. The gene expression of MMP-1 (collagenase-1) and TIMP-1, the protein expression of MMP-1, MMP-2 (gelatinase-A), TIMP-1 and TIMP-2 as well as the enzyme activity of MMP-1 and MMP-2 were examined. AGR and vitamins C and E were shown to reduce MMP expression and activity, whereas 8-prenylnaringenine appeared to be responsible for the opposite effect. None of the substances considerably influenced the TIMP levels. AGR represented the most effective additive in reducing the collagenase protein expression to 60% and may be useful to level out the MMP activity in the skin after sun exposure. Furthermore, no protein expression of MMP-8, MMP-9, MMP-12 and MMP-13 could be detected.