The Dietary Pigment Curcumin Reduces Endothelial Tissue Factor Gene Expression by Inhibiting Binding of AP-1 to the DNA and Activation of NF-κB

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Abstract
The natural occurring pigment curcumin, a major component of the spice tumeric, has been described to have antioxidative, antitumorpro moting, anti-thrombotic and anti-inflammatory properties. It appears, that the pleiotropic effects of curcumin are at least partly due to inhibi tion of the transcription factors NF-κB and AP-1. This study investi gates the effect of curcumin on the TNFa induced expression of endo thelial Tissue Factor (TF), the central mediator of coagulation known to be controlled by AP-1 and NF-κ When bovine aortic endothelial cells (B AEC) were preincubated in the presence of curcumin, TNFα induced TF gene transcription and expression were reduced. Transient transfec tion studies with TF-promoter plasmids revealed that both, NF-κ and AP-1 dependent TF expression, were reduced by curcumin action. The observed inhibitions were due to distinct mechanisms. Curcumininhib ited TNFa induced kBa degradation and the nuclear import of NF-κB. In contrast, inhibition of AP-1 was due to a direct interaction of curcu min with AP-1-binding to its DNA binding motif. Thus, curcumin inhibits NF-κB and AP-1 by two different mechanisms and reduces expression of endothelial genes controlled by both transcription factors in vitro.

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