The dietary pigment curcumin reduces endothelial tissue factor gene expression by inhibiting binding of AP-1 to the DNA and activation of NF-kappa B.
The natural occurring pigment curcumin, a major component of the spice tumeric, has been described to have antioxidative, anti-tumorpromoting, anti-thrombotic and anti-inflammatory properties. It appears, that the pleiotropic effects of curcumin are at least partly due to inhibition of the transcription factors NF-kappa B and AP-1. This study investigates the effect of curcumin on the TNF alpha induced expression of endothelial Tissue Factor (TF), the central mediator of coagulation known to be controlled by AP-1 and NF-kappa B. When bovine aortic endothelial cells (BAEC) were preincubated in the presence of curcumin, TNF alpha induced TF gene transcription and expression were reduced. Transient transfection studies with TF-promoter plasmids revealed that both, NF-kappa B and AP-1 dependent TF expression, were reduced by curcumin action. The observed inhibitions were due to distinct mechanisms. Curcumin inhibited TNF alpha induced I kappa B alpha degradation and the nuclear import of NF-kappa B. In contrast, inhibition of AP-1 was due to a direct interaction of curcumin with AP-1-binding to its DNA binding motif. Thus, curcumin inhibits NF-kappa B and AP-1 by two different mechanisms and reduces expression of endothelial genes controlled by both transcription factors in vitro.
Bierhaus
A
A
Department of Internal Medicine I, University of Heidelberg, Germany.
Zhang
Y
Y
Quehenberger
P
P
Luther
T
T
Haase
M
M
Müller
M
M
Mackman
N
N
Ziegler
R
R
Nawroth
P P
PP
D000818:Animals; D002417:Cattle; D004396:Coloring Agents; D003474:Curcumin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004032:Diet; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013925:Thromboplastin / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D004396:Coloring Agents; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin; D003474:Curcumin