TNFalpha-induced NF-kappaB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells

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

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

Elsevier inc.

Lugar: EEUU; Año: 2008

0003-9861

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