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 TNF?

Abstract

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.

Inhibition of Autoantigen Expression by (-)-Epigallocatechin-3-gallate (the Major Constituent of Green Tea) in Normal Human Cells

“…The inhibition of IL-1␤ signaling may occur through the modulation of the mitogen-activated protein kinase pathway components . Green tea and EGCG are able to inhibit IL-8 release in TNF-␣-stimulated NHEK (Trompezinski et al, 2003). A recent study showed that EGCG suppressed lipopolysaccharide-induced dendritic cell maturation, therefore reducing the subsequent T cell activation (Ahn et al, 2004).…”

Green tea and the skin

“…71 In addition, tumor necrosis factor a-induced IL-8 release was dose-dependently inhibited by EGCG in cultured NHEKs, whereas vascular epithelial growth factor was stimulated. 72 Another study demonstrated that TPA-induced IL-1 expression was significantly inhibited by GTPPs. 73 In mouse epidermal cells, EGCG inhibited TPAinduced NF kB activation by blocking phosphorylation of IkBa (inhibitor of NF kB) at Ser32 and inhibited the DNA binding of NF kB.…”

The possibility of genistein as a new direct pulp capping agent

“…We had investigated the inflammation rate of the pulp after operation, low concentration group was minor inflammation compared to the control. It has been reported that genistein may reduce inflammation via inhibition of cyclooxygenase activity 38,39) , and inhibition of vascular permeability by suppressing the expression of VEGF and its receptor gene 40,41) , we considered that suppression of inflammation in these same mechanisms. So, we supposed that improvement of covering degree is induced by short-term reducing inflammation.…”