Abstract
Hexameric procyanidins inhibit TNFα-induced NF-κB 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-κB 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 (TNFα)-induced NF-κB activation as related to oxidation and membrane interactions. In Caco-2 cells, Hex (2.5-20 μM) inhibited TNFα-induced NF-κB activation (IκB phosphorylation and degradation, p50 and RelA nuclear translocation, and NF-κB-DNA binding), inducible nitric oxide synthase expression, and cell oxidant increase. The effects on NF-κB activation persist beyond the period of direct exposition of cells to Hex. N-Acetylcysteine and α-lipoic acid inhibited TNFα-induced oxidant increase but did not affect NF-κB activation. In summary, Hex can inhibit NF-κB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFα to its receptor and the subsequent NF-κB activation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 186-195 |
| Number of pages | 10 |
| Journal | Archives of Biochemistry and Biophysics |
| Volume | 476 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 15 2008 |
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Keywords
- Antioxidant
- Cocoa
- Flavanol
- Flavonoid
- Gastrointestinal tract
- Inflammation
- Intestinal barrier
- Membrane interactions
- Procyanidin
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
TNFα-induced NF-κB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells. / Erlejman, Alejandra G.; Jaggers, Grayson; Fraga, Cesar G.; Oteiza, Patricia I.
In: Archives of Biochemistry and Biophysics, Vol. 476, No. 2, 15.08.2008, p. 186-195.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TNFα-induced NF-κB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells
AU - Erlejman, Alejandra G.
AU - Jaggers, Grayson
AU - Fraga, Cesar G.
AU - Oteiza, Patricia I.
PY - 2008/8/15
Y1 - 2008/8/15
N2 - Hexameric procyanidins inhibit TNFα-induced NF-κB 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-κB 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 (TNFα)-induced NF-κB activation as related to oxidation and membrane interactions. In Caco-2 cells, Hex (2.5-20 μM) inhibited TNFα-induced NF-κB activation (IκB phosphorylation and degradation, p50 and RelA nuclear translocation, and NF-κB-DNA binding), inducible nitric oxide synthase expression, and cell oxidant increase. The effects on NF-κB activation persist beyond the period of direct exposition of cells to Hex. N-Acetylcysteine and α-lipoic acid inhibited TNFα-induced oxidant increase but did not affect NF-κB activation. In summary, Hex can inhibit NF-κB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFα to its receptor and the subsequent NF-κB activation.
AB - Hexameric procyanidins inhibit TNFα-induced NF-κB 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-κB 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 (TNFα)-induced NF-κB activation as related to oxidation and membrane interactions. In Caco-2 cells, Hex (2.5-20 μM) inhibited TNFα-induced NF-κB activation (IκB phosphorylation and degradation, p50 and RelA nuclear translocation, and NF-κB-DNA binding), inducible nitric oxide synthase expression, and cell oxidant increase. The effects on NF-κB activation persist beyond the period of direct exposition of cells to Hex. N-Acetylcysteine and α-lipoic acid inhibited TNFα-induced oxidant increase but did not affect NF-κB activation. In summary, Hex can inhibit NF-κB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFα to its receptor and the subsequent NF-κB activation.
KW - Antioxidant
KW - Cocoa
KW - Flavanol
KW - Flavonoid
KW - Gastrointestinal tract
KW - Inflammation
KW - Intestinal barrier
KW - Membrane interactions
KW - Procyanidin
UR - http://www.scopus.com/inward/record.url?scp=48049104552&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=48049104552&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2008.01.024
DO - 10.1016/j.abb.2008.01.024
M3 - Article
VL - 476
SP - 186
EP - 195
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
SN - 0003-9861
IS - 2
ER -