Modulation of signalling nuclear factor-κB activation pathway by polyphenols in human intestinal Caco-2 cells

Abstract

Recent studies support beneficial effects of polyphenols in various chronic inflammatory diseases, for example, the inflammatory bowel diseases. Inhibition of NF-kappaB activation by polyphenols could explain part of their anti-inflammatory properties, but few data are available on the intestine. The purpose of the present study was thus to investigate the effects of some polyphenols on NF-kappaB activation using human intestinal Caco-2 cells. Effects of standard polyphenols (50 mumol/l) were studied on different cellular events associated with NF-kappaB activation: (i) NF-kappaB activity using cells transiently transfected with a NF-kappaB-luciferase construct and stimulated by inflammatory agents (IL-1beta, TNF-alpha or lipopolysaccharides (LPS)); (ii) phosphorylation of the inhibitor of kappaB (IkappaB-alpha) analysed by Western blot; (iii) secretion of IL-8 quantified by ELISA assay. Results showed that chrysin and ellagic acid inhibited NF-kappaB activity, whereas genistein and resveratrol increased it. These effects were independent of the nature of the inducer, indicating that polyphenols may modulate NF-kappaB activation by acting on a common event to the cytokine- and LPS-mediated cascades. Chrysin strongly reduced (2.5-fold) IL-1beta-induced IkappaB-alpha phosphorylation, whereas ellagic acid increased it (1.7-fold). Ellagic acid, genistein and epigallocatechin gallate reduced (4- to 8-fold) IL-1beta-induced IL-8 secretion, while resveratrol promoted (1.7-fold) the secretion. Chrysin also diminished IL-8 secretion by 1.6-fold (but P>0.05). The data indicate that polyphenols can modulate the NF-kappaB activation pathway in the intestine. Chrysin could block NF-kappaB activation via the inhibition of IkappaB-alpha phosphorylation. The other molecular targets of the active polyphenols are still to be identified.