Gingko biloba extract reduces VEGF and CXCL-8/IL-8 levels in keratinocytes with cumulative effect with epigallocatechin-3-gallate.

In skin inflammation, vascular endothelial growth factor (VEGF) and CXCL-8/IL-8 play an important role and are produced by activated keratinocytes. Extracts from Ginkgo biloba leaves (GBE), widely used in phytotherapy, have been reported to exert antioxidant and anti-inflammatory properties in the skin. We therefore evaluated the effects of GBE on the release of VEGF and CXCL8/IL-8 by normal human keratinocytes (NHKs) activated by tumor necrosis factor alpha (TNFalpha). Moreover, as we previously showed that epigallocatechin-3-gallate (EGCG) reduces VEGF and CXCL8/IL-8 secretion in TNFalpha-activated NHKs, we also tested its effect in association with GBE. Our results showed that GBE exerted a potent inhibition on VEGF and CXCL8/IL-8 levels in activated cells. In association with EGCG, GBE down-regulated VEGF and CXCL8/IL-8 levels in a cumulative manner in TNFalpha-stimulated NHKs. These results suggest that GBE, alone or in association with EGCG may contribute to moderate inflammatory processes in skin diseases associated with angiogenesis.

Role of sugars in surface microbe-host interactions and immune reaction modulation.

Sugars in the form of monosaccharides, oligosaccharides, polysaccharides and glycoconjugates (glycoproteins, glycolipids) are vital components of infecting microbes and host cells, and are involved in cell signalling associated with modulation of inflammation in all integumental structures. Indeed, sugars are the molecules most commonly involved in cell recognition and communication. In skin, they are essential to epidermal development and homeostasis. They play important roles in microbial adherence, colonization and biofilm formation, and in virulence. Two groups of pathogen recognition receptors, C-type lectins (CTL) and their receptors (CTLR), and the Toll-like receptors enable the host to recognize pathogen-associated molecular patterns (PAMPs), which are mainly glycolipids. The CTLs can recognize a wide variety of bacteria, fungi and parasites and are important in phagocytosis and endocytosis. TLRs are expressed on the surfaces of a variety of cells, including keratinocytes, dendritic cells, monocytes and macrophages; they play a major role in innate immunity. Interaction of TLRs with PAMPs initiates a cascade of events leading to production of reactive oxygen intermediates, cytokines and chemokines, and promotes inflammation. Exogenous sugars can block carbohydrate receptors and competitively displace bacteria from attachment to cells, including keratinocytes. Thus sugars may provide valuable adjunctive anti-inflammatory and/or antimicrobial treatment. A promising approach is the use of a panel of carbohydrate derivatives with anti-adhesive efficacy against bacteria frequently involved in diseases affecting skin and other epithelia. More complete characterization of sugar receptors and their ligands will provide further keys to use of carbohydrates in immunomodulation and infection control in skin.

Comparative effects of polyphenols from green tea (EGCG) and soybean (genistein) on VEGF and IL-8 release from normal human keratinocytes stimulated with the proinflammatory cytokine TNFalpha.

In skin inflammation, vascular endothelial growth factor (VEGF) and IL-8 play an important role and are produced by activated keratinocytes. Recently, some polyphenols have been reported to exhibit antiinflammatory and antiangiogenic properties. We therefore evaluated the effects of green tea, its major component epigallocatechin-3-gallate (EGCG) and an isoflavone derived from soybean (genistein) on the release of VEGF and IL-8 by activated normal human keratinocytes (NHK). NHK cultured in defined medium were stimulated for 48 h with the proinflammatory cytokine TNFalpha with the addition or not of different concentrations of polyphenols. Levels of VEGF and IL-8 were measured in cell supernatants by enzyme-linked immunosorbent assays. The different constituents tested inhibited keratinocyte proliferation without inducing apoptosis. They reduced in a dose-dependent manner the basal release and the upregulation of VEGF in NHK. Green tea and EGCG were also potent inhibitors of IL-8 release by TNFalpha-stimulated NHK, whereas genistein exerted only minor effects. These results underline the divergent pathways involved in the downregulation of VEGF and IL-8 by polyphenols in activated keratinocytes. They also suggest that polyphenols may contribute to moderate inflammatory processes in skin diseases associated with angiogenesis.