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 microM 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.


CONCLUSIONS
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.
Suganuma
Kaoru
K
Department of Dermatology, Jichi Medical University, 3311-1 Yakushiji, Shimotuke, Tochigi 329-0498, Japan.
Nakajima
Hiroaki
H
Ohtsuki
Mamitaro
M
Imokawa
Genji
G
D002470:Cell Survival; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D015260:Neprilysin / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology* / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation; D024341:Xanthophylls / Q000494:pharmacology
D017931:DNA Primers; D024341:Xanthophylls; C005948:astaxanthine; D010196:Pancreatic Elastase; D015260:Neprilysin; D020781:Matrix Metalloproteinase 1