Summary
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.
