TNFa-induced NF-kB activation and cell oxidant production

A. G. ERLEJMAN; G. JAGGERS; C. G. FRAGA; P. I. OTEIZA

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

Elsevier

Año: 2008 vol. 476 p. 186 - 195

0003-9861

Hexameric procyanidins inhibit TNFa-induced NF-jB 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-jB 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 (TNFa)-induced NF-jB activation as related to oxidation and membrane interactions. In Caco-2 cells, Hex (2.5–20 lM) inhibited TNFa-induced NF-jB activation (IjB phosphorylation and degradation, p50 and RelA nuclear translocation, and NF-jB–DNA binding), inducible nitric oxide synthase expression, and cell oxidant increase. The effects on NF-jB activation persist beyond the period of direct exposition of cells to Hex. N-Acetylcysteine and a-lipoic acid inhibited TNFa-induced oxidant increase but did not affect NF-jB activation. In summary, Hex can inhibit NF-jB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFa to its receptor and the subsequent NF-jB activation.a-induced NF-jB 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-jB 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 (TNFa)-induced NF-jB activation as related to oxidation and membrane interactions. In Caco-2 cells, Hex (2.5–20 lM) inhibited TNFa-induced NF-jB activation (IjB phosphorylation and degradation, p50 and RelA nuclear translocation, and NF-jB–DNA binding), inducible nitric oxide synthase expression, and cell oxidant increase. The effects on NF-jB activation persist beyond the period of direct exposition of cells to Hex. N-Acetylcysteine and a-lipoic acid inhibited TNFa-induced oxidant increase but did not affect NF-jB activation. In summary, Hex can inhibit NF-jB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFa to its receptor and the subsequent NF-jB activation.jB 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 (TNFa)-induced NF-jB activation as related to oxidation and membrane interactions. In Caco-2 cells, Hex (2.5–20 lM) inhibited TNFa-induced NF-jB activation (IjB phosphorylation and degradation, p50 and RelA nuclear translocation, and NF-jB–DNA binding), inducible nitric oxide synthase expression, and cell oxidant increase. The effects on NF-jB activation persist beyond the period of direct exposition of cells to Hex. N-Acetylcysteine and a-lipoic acid inhibited TNFa-induced oxidant increase but did not affect NF-jB activation. In summary, Hex can inhibit NF-jB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFa to its receptor and the subsequent NF-jB activation.a)-induced NF-jB activation as related to oxidation and membrane interactions. In Caco-2 cells, Hex (2.5–20 lM) inhibited TNFa-induced NF-jB activation (IjB phosphorylation and degradation, p50 and RelA nuclear translocation, and NF-jB–DNA binding), inducible nitric oxide synthase expression, and cell oxidant increase. The effects on NF-jB activation persist beyond the period of direct exposition of cells to Hex. N-Acetylcysteine and a-lipoic acid inhibited TNFa-induced oxidant increase but did not affect NF-jB activation. In summary, Hex can inhibit NF-jB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFa to its receptor and the subsequent NF-jB activation.a-induced NF-jB activation (IjB phosphorylation and degradation, p50 and RelA nuclear translocation, and NF-jB–DNA binding), inducible nitric oxide synthase expression, and cell oxidant increase. The effects on NF-jB activation persist beyond the period of direct exposition of cells to Hex. N-Acetylcysteine and a-lipoic acid inhibited TNFa-induced oxidant increase but did not affect NF-jB activation. In summary, Hex can inhibit NF-jB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFa to its receptor and the subsequent NF-jB activation.jB activation persist beyond the period of direct exposition of cells to Hex. N-Acetylcysteine and a-lipoic acid inhibited TNFa-induced oxidant increase but did not affect NF-jB activation. In summary, Hex can inhibit NF-jB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFa to its receptor and the subsequent NF-jB activation.N-Acetylcysteine and a-lipoic acid inhibited TNFa-induced oxidant increase but did not affect NF-jB activation. In summary, Hex can inhibit NF-jB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFa to its receptor and the subsequent NF-jB activation.jB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFa to its receptor and the subsequent NF-jB activation.a to its receptor and the subsequent NF-jB activation.