title: Resveratrol enhances solar UV-induced responses in normal human epidermal keratinocytes.
abstract: Resveratrol (RV) differentially affects UV-induced death/pro-survival pathways in normal and tumor cells. On these grounds, RV-containing topical products have been developed to prevent UV-associated tumorigenesis/damage to human skin. In this study, we evaluated mechanisms of combined effects of RV and low-dose solar simulated UVA+UVB or 6-formylindo[3,2-b]carbazole (FICZ), a product of tryptophan photo-oxidation known to mediate UV effects, on the inflammatory, metabolic and proliferative responses of cultured normal human epidermal keratinocytes (HEK). Applied alone, RV, UV and FICZ induced time- and dose-dependent activation of aryl hydrocarbon receptor (AhR) pathway followed by over-expression of Cyp1A1 (metabolic response), UV and RV induced IL-8 expression (inflammatory response), while RV enhanced also HEK proliferation revealed by MTT assay and (3)H-thymidine incorporation. In the combined treatment, RV synergized with both UV and FICZ, leading to further activation of AhR machine, Cyp1A1 transcription and IL-8 expression, the latter partly AhR-dependent as assessed by AhR silencing. RV enhanced UV-induced NFkappaB activation and nuclear translocation of epidermal growth factor receptor. By contrast, proliferative effect of RV was abolished in the presence of UV, whereas synergic anti-proliferative action of RV+UV was observed in the Nrf2-silenced HEK. Our data suggest cooperative effects of RV-specific and UV-/FICZ-activated transcription factors leading to deregulated inflammatory, metabolic and proliferative responses of HEK.
authors: Laboratory of Tissue Engineering and Skin Pathophysiology, Dermatology Institute (Istituto Dermopatico dell'Immacolata, IDI IRCCS), Rome, Italy.
authors: Saveria
authors: S
authors: Pastore
authors: Daniela
authors: D
authors: Lulli
authors: Antonia
authors: A
authors: Pascarella
authors: Riccardo
authors: R
authors: Maurelli
authors: Elena
authors: E
authors: Dellambra
authors: Alla
authors: A
authors: Potapovich
authors: Vladimir
authors: V
authors: Kostyuk
authors: Chiara
authors: C
authors: De Luca
authors: Liudmila
authors: L
authors: Korkina
mesh_terms: D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D000078404:Epidermal Cells; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000528:radiation effects*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013472:Sunlight; D014466:Ultraviolet Rays
chemical_list: D016209:Interleukin-8; D013267:Stilbenes; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; D000077185:Resveratrol