Abstracts
Background
The understanding of the anti-inflammatory mechanisms of action of plant polyphenols (PPs) and clarification of the relationship between their anti-inflammatory and antioxidant properties may result in a new therapeutic approach to skin cancers.
Objective
To elucidate the underlying mechanism, we analyzed the ability of PPs to attenuate inflammatory, metabolic and oxidative cellular responses to UV irradiation.
Methods
Normal human epidermal keratinocytes (NHEK) were exposed to physiologically relevant dose of solar-simulated UV irradiation. Effects of pre- and post-treatment with PPs on the overproduction of peroxides and inflammatory mediators (mRNA and protein) were analyzed using real-time RT-PCR, enzyme-linked immunosorbent and fluorometric techniques.
Results
Differences between the effectiveness of pre- and post-treatment with polyphenols was found. In particular, PPs post-treatment, but not pretreatment, completely abolished overexpression of Cyp1a1 and Cyp1b1 genes and elevation of intracellular peroxides in NHEK irradiated by UV. Post-treatment with PPs also more efficiently than pretreatment prevented UV-induced overexpression of IL-1 beta, IL-6 and COX2 mRNAs.
Conclusion
Our data strongly suggest that PPs predominantly affect delayed molecular and cellular events initiated in NHEK by solar UV rather than primary photochemical reactions. PPs may be important component in cosmetic formulations for post-sun skin care.
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References
De Gruijl FR. Skin cancer and solar UV radiation. Eur J Cancer. 1999;35:2003–9.
Aitken GR, Henderson JR, Chang SC, McNeil CJ, Birch-Machin MA. Direct monitoring of UV-induced free radical generation in HaCaT keratinocytes. Clin Exp Dermatol. 2007;32:722–7.
Valencia A, Kochevar IE. Nox1-based NADPH oxidase is the major source of UVA-induced reactive oxygen species in human keratinocytes. J Invest Dermatol. 2008;128:214–22.
Sachsenmaier C, Radler-Pohl A, Muller A, Herrlich P, Rahmsdorf HJ. Damage to DNA by UV light and activation of transcription factors. Biochem Pharmacol. 1994;47:129–36.
Grether-Beck S, Olaizola-Horn S, Schmitt H, Grewe M, Jahnke A, Johnson JP, Briviba K, Sies H, Krutmann J. Activation of transcription factor AP-2 mediates UVA radiation and singlet oxygen-induced expression of the human intercellular adhesion molecule 1 gene. Proc Natl Acad Sci USA. 1996;93:14586–91.
Mahns A, Wolber R, Stab F, Klotz LO, Sies H. Contribution of UVB and UVA to UV-dependent stimulation of cyclooxygenase-2 expression in artificial epidermis. Photochem Photobiol Sci. 2004;3:257–62.
Belli R, Amerio P, Brunetti L, Orlando G, Toto P, Proietto G, Vacca M, Tulli A. Elevated 8-isoprostane levels in basal cell carcinoma and in UVA irradiated skin. Int J Immunopathol Pharmacol. 2005;18:497–502.
Pastore S, Mascia F, Mariani V, Girolomoni G. The epidermal growth factor receptor system in skin repair and inflammation. J Invest Dermatol. 2008;128:1365–74.
Korkina LG, Pastore S, De Luca C, Kostyuk VA. Metabolism of plant polyphenols in the skin: beneficial versus deleterious effects. Curr Drug Metab. 2008;9:10–29.
Klebanoff SJ. Myeloperoxidase-halide-hydrogen peroxide antibacterial system. J Bacteriol. 1968;95:2131–8.
Adams DO, Hamilton TA. Macrophages as destructive cells in host defense. In: Gallin JI, Goldstein IM, Synderman R, editors. The Inflammation: basic principles and clinical correlates. New York: Raven Press; 1992. pp. 637–662.
Baumann H, Gauldie J. The acute phase response. Immunol Today. 1994;15:74–80.
Shacter E, Beecham EJ, Covey JM, Kohn KW, Potter M. Activated neutrophils induce prolonged DNA damage in neighboring cells. Carcinogenesis. 1988;9:2297–304.
Brigelius-Flohé R, Flohé L. Basic principles and emerging concepts in the redox control of transcription factors. Antioxid Redox Signal. 2011;15:2335–81.
Tunon MJ, Garcia-Mediavilla MV, Sanchez-Campos S, Gonzalez-Gallego J. Potential of flavonoids as anti-inflammatory agents: modulation of pro-inflammatory gene expression and signal transduction pathways. Curr Drug Metab. 2009;10:256–71.
Vanden Berghe W, Haegeman G. Epigenetic remedies by dietary phytochemicals against inflammatory skin disorders: myth or reality? Curr Drug Metab. 2010;11:436–50.
Nichols JA, Katiyar SK. Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res. 2010;302:71–83.
Liu ML, Yu LC. Potential protection of green tea polyphenols against ultraviolet irradiation-induced injury on rat cortical neurons. Neurosci Lett. 2008;444:236–9.
Wu LY, Zheng XQ, Lu JL, Liang YR. Protective effect of green tea polyphenols against ultraviolet B-induced damage to HaCaT cells. Hum Cell. 2009;22:18–24.
Vicentini FTMC, He T, Shao Y, Fonseca MJV, Verri WA, Fisher GJ, Xu Y. Quercetin inhibits UV irradiation-induced inflammatory cytokine production in primary human keratinocytes by suppressing NF-kB pathway. J Dermatol Sci. 2011;61:162–8.
Pastore S, Potapovich A, Lulli D, Fidanza P, Kostyuk V, De Luca C, Mikhal’chik E, Korkina L. Plant polyphenols regulate chemokine expression and tissue repair in human keratinocytes through interaction with cytoplasmic and nuclear components of epidermal growth factor receptor (EGFR) system. Antioxid Redox Signal. 2012;16:314–28.
Pastore S, Lulli D, Potapovich AI, Fidanza P, Kostyuk VA, Dellambra E, de Luca C, Maurelli R, Korkina LG. Differential modulation of stress-inflammation responses by plant polyphenols in cultured normal human keratinocytes and immortalized HaCaT cells. J Dermatol Sci. 2011;63:104–14.
Adhami VM, Afaq F, Ahmad N. Suppression of ultraviolet B exposure-mediated activation of NFkappaB in normal human keratinocytes by resveratrol. Neoplasia. 2003;5:74–82.
Kojima H, Nakatsubo N, Kikuchi K, Kawahara S, Kirino Y, Nagoshi H, Hirata Y, Nagano T. Detection and imaging of nitric oxide with novel fluorescent indicators: diaminofluoresceins. Anal Chem. 1998;70:2446–53.
Kooy NW, Royall JA, Ischiropoulos H, Beckman JS. Peroxynitrite-mediated oxidation of dihydrorhodamine 123. Free Radic Biol Med. 1994;16:149–56.
Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA. 1990;87:1620–4.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using realtime quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402–8.
Kostyuk VA, Potapovich AI, Lulli D, Stancato A, De Luca C, Pastore S, Korkina L. Modulation of human keratinocyte responses to solar UV by plant polyphenols as a basis for chemoprevention of non-melanoma skin cancers. Curr Med Chem. 2013;20:869–79.
Afaq F, Katiyar SK. Polyphenols: skin photoprotection and inhibition of photocarcinogenesis. Mini Rev Med Chem. 2011;11:1200–15.
Wu S, Wang L, Jacoby AM, Jasinski K, Kubant R, Malinski T. Ultraviolet B light-induced nitric oxide/peroxynitrite imbalance in keratinocytes-implications for apoptosis and necrosis. Photochem Photobiol. 2010;86:389–96.
Acknowledgments
The work was partly financed by the grant from Italian Ministry for Health (RC. IDI IRCCS-2012).
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Responsible Editor: Helen Griffiths.
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Potapovich, A.I., Kostyuk, V.A., Kostyuk, T.V. et al. Effects of pre- and post-treatment with plant polyphenols on human keratinocyte responses to solar UV. Inflamm. Res. 62, 773–780 (2013). https://doi.org/10.1007/s00011-013-0634-z
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DOI: https://doi.org/10.1007/s00011-013-0634-z