Modulation of signalling nuclear factor-kappaB activation pathway by polyphenols in human intestinal Caco-2 cells.
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.
Romier
Béatrice
B
Biochimie Cellulaire, Nutritionnelle and Toxicologique, Institut des Sciences de la Vie and Université Catholique de Louvain, Louvain-la-Neuve B 1348, Belgium.
Van De Walle
Jacqueline
J
During
Alexandrine
A
Larondelle
Yvan
Y
Schneider
Yves-Jacques
YJ
D015415:Biomarkers / Q000032:analysis; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005419:Flavonoids / Q000627:therapeutic use*; D006801:Humans; D020672:I-kappa B Proteins / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008070:Lipopolysaccharides; D008156:Luciferases / Q000032:analysis; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010636:Phenols / Q000627:therapeutic use*; D010766:Phosphorylation; D059808:Polyphenols; D015398:Signal Transduction / Q000187:drug effects*
D015415:Biomarkers; D005419:Flavonoids; D020672:I-kappa B Proteins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D010636:Phenols; D059808:Polyphenols; D000072000:NF-KappaB Inhibitor alpha; D007770:L-Lactate Dehydrogenase; D008156:Luciferases