Proinflammatory effect of cholesterol and its oxidation products on CaCo-2 human enterocyte-like cells effective protection by epigallocatechin-3-gallate

Cholesterol and its oxidation products namely oxysterols have very recently been shown to potentially interfere with homeostasis of the human digestive tract by promoting and sustaining irreversible damage of the colonic epithelial layer This report concerns the strong proinflammatory action that a dietary oxysterol mixture and to a lesser extent an identical concentration of unoxidized cholesterol exert on CaCo-2 colonic epithelial cells by up-regulating both expression and synthesis of interleukin 8 The oxysterol mixture and its most effective component 7 beta-hydroxycholesterol are also shown to markedly enhance the expression of key inflammatory and chemotactic cytokines in colonic epithelial cells more efficiently than unoxidized cholesterol The sterols proinflammatory effect seems to be mediated by enhanced activation of NOX1 because It is prevented by pretreatment of the cells with DPI a selective inhibitor of this oxidase Importantly NOX1 hyperactivation by the oxysterol mixture or cholesterol was fully prevented by CaCo-2 cell preincubation with epigallocatechin-3 gallate Consistently supplementation with this compound fully protected colonic epithelial cells against overexpression of inflammatory and chemotactic genes induced by the sterols investigated (C) 2010 Elsevier Inc All rights reserved