(-)Epigallocatechin gallate hampers collagen destruction and collagenase activation in ultraviolet-B-irradiated human dermal fibroblasts: involvement of mitogen-activated protein kinase.

摘要

Ultraviolet (UV) irradiation leads to distinct changes in skin connective tissues by degradation of collagen, which is a major structural component in the extracellular matrix most likely mediated by matrix metalloproteinases (MMP), collagenases. These changes in collagenous skin tissues have been suggested to be causes of the skin wrinkling observed in premature aging of the skin. This study mimicked the action of environmental ultraviolet on skin and investigated whether (-)epigallocatechin gallate (EGCG), a bioactive catechin component of green tea, mechanistically inhibited activation of MMP-1, MMP-8, and MMP-13 and destruction of collagen in UV-B irradiated human dermal fibroblasts by modulating cellular signaling pathways. Cell viability was moderately decreased by > or = 30% in human dermal fibroblasts treated with 100 mJ/cm2 UV-B, accompanying a substantial generation of reactive oxygen species evidenced by DCF staining. Western blot analysis and immunocytochemical staining revealed that EGCG markedly suppressed collagen degradation enhanced in UV-B-exposed human dermal fibroblast. Pre-treatment of fibroblasts with EGCG also inhibited UV-B-induced production of collagenases, MMP-1, MMP-8 and MMP-13, in a dose-dependent manner. In addition, EGCG rapidly and substantially hampered UV-B irradiation-induced activation of ASK-1 and phosphorylation of MAPK, JNK, p38 MAPK, and ERK1/2, in dermal fibroblasts. These results demonstrate that EGCG has abilities to hamper UV-B-induced collagenolytic MMP production via interfering with the MAPK-responsive pathways. Therefore, EGCG may be a potential agent for the prevention and treatment of skin photoaging.