UV-induced NF-κB activation and expression of IL-6 is attenuated by (-)-epigallocatechin-3-gallate in cultured human keratinocytes in vitro

Abstract

Ultraviolet (UV) radiation from the sun is widely considered as a major cause of human skin photoaging and skin cancer. UV radiation-induced proinflammatory cytokines mediated by NF-kappaB reportedly play important roles in photoaging and cancer. NF-kappaB and cytokines have been thus perceived as molecular targets for pharmacological intervention. With an increasing amount of knowledge of the actions of green tea extracts at cellular and molecular levels, the beneficial effect of drinking green tea has become well recognized if not completely accepted. The components in green tea have even been added to skin-care products unregulated, while the molecular mechanisms of the actions of those components on human skin are being unraveled. Using cultured human keratinocytes, we investigated the effects of (-)-epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent in green tea, on UV-induced activation of transcription factor NF-kappaB and proinflammatory pathway by measuring nuclear translocation of NF-kappaB and IL-6 secretion in vitro. Immunohistochemical and Western blot analysis and ELISA indicated that both nuclear p65 and secreted IL-6 were significantly (p<0.05) induced by UVB (20, 30 mJ/cm2) and UVA irradiation (10, 20 J/cm2). NF-kappaB nuclear translocation and IL-6 secretion induced by UVB and UVA were dramatically inhibited by treatment of EGCG. FACS analysis showed that EGCG also inhibited UVB-induced apoptosis. EGCG recovered UV-induced loss of anti-apoptotic component, bcl-2, and inhibited UV-induced apoptotic component, Fas ligand, expression. Collectively, we conclude that EGCG inhibits UVB- and UVA-induced proinflammatory pathway and inhibits apoptosis in cultured human keratinocytes in vitro. Our data suggest that EGCG be added to cosmetic or skin-care products for prevention from UV-induced skin photoaging if this activity can be further confirmed and no cytotoxicity is reported in human skin in vivo.