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

• Published in: British journal of nutrition 2008-09, Vol.100 (3), p.542-551
• Main Authors: Romier, Béatrice, Van De Walle, Jacqueline, During, Alexandrine, Larondelle, Yvan, Schneider, Yves-Jacques
• Format: Article
• Language: English
• Subjects: Biomarkers - analysis; Caco-2 Cells; Cell Proliferation - drug effects; Colitis - drug therapy; Colitis - immunology; Colitis - metabolism; Colon - drug effects; Colon - immunology; Colon - metabolism; Flavonoids - therapeutic use; Humans; I-kappa B Proteins - analysis; Interleukin-8 - analysis; Interleukin-8 - secretion; L-Lactate Dehydrogenase - analysis; Lipopolysaccharides; Luciferases - analysis; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; Phenols - therapeutic use; Phosphorylation; Polyphenols; Signal Transduction - drug effects
• ISSN: 1475-2662
• DOI: 10.1017/S0007114508966666

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.