Astaxanthin attenuates the UVA-induced up-regulation of matrix-metalloproteinase-1 and skin fibroblast elastase in human dermal fibroblasts

Background: Repetitive exposure of the skin to UVA radiation elicits sagging more frequently than wrinkling, which is mainly attributed to its biochemical mechanism to up-regulate the expression of matrix-metalloproteinase (MMP)-1 and skin fibroblast elastase (SFE)/neutral endopeptidase (NEP), respectively. Objective: In this study, we examined the effects of a potent antioxidant, astaxanthin (AX), on the induction of MMP-1 and SFE by UVA treatment of cultured human dermal fibroblasts. Methods: Those effects were assessed by real-time RT-PCR. Western blotting and enzymic activity assays. Results: UVA radiation elicited a significant increase in the gene expression of MMP-1 as well as SFE/NEP (to a lesser extent) which was followed by distinct increases in their protein and enzymatic activity levels. The addition of AX at concentrations of 4-8 mu M immediately after UVA exposure significantly attenuated the induction of MMP-1 and SFE/NEP expression elicited by UVA at the gene, protein and activity levels although both the UVA stimulation and the subsequent AX inhibition were greater for MMP-1 than for SFE/NEP. Analysis of the UVA-induced release of cytokines revealed that UVA significantly stimulated only the secretion of IL-6 among the cytokines tested and that AX significantly diminished only the IL-6 secretion. Conclusion: These findings indicate that, based on different effective concentrations of AX, a major mode of action leading to the inhibition elicited by AX depends on inhibition of UVA effects of the reactive oxygen species-directed signaling cascade, but not on interruption of the IL-6-mediated signaling cascade. We hypothesize that AX would have a significant benefit on protecting against UVA-induced skin photo-aging such as sagging and wrinkles. (c) 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.