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Resveratrol Enhances Solar UV‐induced Responses in Normal Human Epidermal Keratinocytes
Author(s) -
Pastore Saveria,
Lulli Daniela,
Pascarella Antonia,
Maurelli Riccardo,
Dellambra Elena,
Potapovich Alla,
Kostyuk Vladimir,
De Luca Chiara,
Korkina Liudmila
Publication year - 2012
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2012.01195.x
Subject(s) - aryl hydrocarbon receptor , chemistry , resveratrol , hek 293 cells , carcinogenesis , transcription factor , microbiology and biotechnology , cancer research , signal transduction , cell growth , receptor , biochemistry , biology , gene
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.