Antioxidants modulate acute solar ultraviolet radiation-induced NF-kappa-Bactivation in a human keratinocyte cell line

Exposure of the human skin to ultraviolet radiation (UVR) leads to depletio n of cutaneous antioxidants, regulation of gene expression and ultimately t o the development of skin diseases. Although exogenous supplementation of a ntioxidants prevents UVR-induced photooxidative damage, their effects on co mponents of cell signalling pathways leading to gene expression has not bee n clearly established. In the present study, the effects of the antioxidant s alpha-lipoic acid, N-acetyl-L-cysteine (NAC) and the flavonoid extract si lymarin were investigated for their ability to modulate the activation of t he transcription factors nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) in HaCaT keratinocytes after exposure to a solar UV simula tor. The activation of NF-kappa B and AP-1 showed a similar temporal patter n: activation was detected 2 h after UV exposure and maintained for up to 8 hr. To determine the capacity of activated NF-kappa B to stimulate transcr iption, NF-kappa B-dependent gene expression was measured using a reporter gene assay. The effects of the antioxidants on NF-kappa B and AP-1 activati on were evaluated 3 h after exposure. While a high concentration of NAC cou ld achieve a complete inhibition, low concentrations of alpha-lipoic acid a nd silymarin were shown to significantly inhibit NF-kappa B activation. In contrast AP-1 activation was only partially inhibited by NAC, and not at al l by alpha-lipoic acid or silymarin. These results indicate that antioxidan ts such as alpha-lipoic acid and silymarin can efficiently modulate the cel lular response to WR through their selective action on NF-kappa B activatio n. (C) 1998 Elsevier Science Inc.