TNFalpha-induced NF-kappaB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells.
Hexameric procyanidins inhibit TNFalpha-induced NF-kappaB activation in Caco-2 cells. Most of the physiological actions of high molecular weight procyanidins could be limited to the gut lumen. Transcription factor NF-kappaB plays a central role in inflammation including human intestinal bowel disease. We investigated the capacity of a hexameric procyanidin fraction (Hex) to prevent tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation as related to oxidation and membrane interactions. In Caco-2 cells, Hex (2.5-20 microM) inhibited TNFalpha-induced NF-kappaB activation (IkappaB phosphorylation and degradation, p50 and RelA nuclear translocation, and NF-kappaB-DNA binding), inducible nitric oxide synthase expression, and cell oxidant increase. The effects on NF-kappaB activation persist beyond the period of direct exposition of cells to Hex. N-Acetylcysteine and alpha-lipoic acid inhibited TNFalpha-induced oxidant increase but did not affect NF-kappaB activation. In summary, Hex can inhibit NF-kappaB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFalpha to its receptor and the subsequent NF-kappaB activation.
Erlejman
Alejandra G
AG
IQUIFIB-Department of Biological Chemistry (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Jaggers
Grayson
G
Fraga
Cesar G
CG
Oteiza
Patricia I
PI
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors; D007413:Intestinal Mucosa / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D016877:Oxidants / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D010766:Phosphorylation / Q000187:drug effects; D044945:Proanthocyanidins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016328:NF-kappa B; D016877:Oxidants; D044945:Proanthocyanidins; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D051550:I-kappa B Kinase