PMID- 9437186
OWN - NLM
STAT- MEDLINE
DCOM- 19980203
LR  - 20190831
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 17
IP  - 12
DP  - 1997 Dec
TI  - Inhibition of tissue factor gene activation in cultured endothelial cells by 
      curcumin. Suppression of activation of transcription factors Egr-1, AP-1, and 
      NF-kappa B.
PG  - 3406-13
AB  - Binding of plasma factor VII(a) to tissue factor (TF) initiates the coagulation 
      cascade. In health, TF is not expressed in endothelial cells. However, 
      endothelial cells express TF in response to lipopolysaccharide (LPS), tumor 
      necrosis factor-alpha (TNF alpha), and other biological stimuli. TF expression by 
      endothelial cells is implicated in thrombotic disorders in patients with a 
      variety of clinical disorders. In the present study, we demonstrate that curcumin 
      (diferulolylmethane), a known anticarcinogenic and anti-inflammatory agent, 
      inhibited phorbol 12-myristate 13-acetate (PMA), LPS, TNF alpha, and 
      thrombin-induced TF activity and TF gene transcription in human endothelial 
      cells. The present data show that curcumin prevented the activation of c-Rel/p65, 
      which is essential for TF gene activation in endothelial cells, by impairing the 
      proteolytic degradation inhibitor protein, I kappa B alpha. The data also show 
      that curcumin downregulated AP-1 binding activity. The present studies are the 
      first to demonstrate that PMA, but not LPS, TNF alpha, and thrombin, induced 
      Egr-1 binding to the second serum-responsive region (SRR-2) of TF promoter and 
      that curcumin inhibited the PMA-induced Egr-1 binding to SRR-2. Overall, the data 
      suggest that the anticarcinogenic and anti-inflammatory properties of curcumin 
      may be related to its ability to inhibit cellular gene expression regulated by 
      transcription factors NF-kappa B, AP-1, and Egr-1.
FAU - Pendurthi, U R
AU  - Pendurthi UR
AD  - Department of Medical Specialties, University of Texas Health Center, Tyler 
      75710, USA. usha@uthct.edu
FAU - Williams, J T
AU  - Williams JT
FAU - Rao, L V
AU  - Rao LV
LA  - eng
GR  - HL-02590/HL/NHLBI NIH HHS/United States
GR  - HL-42813/HL/NHLBI NIH HHS/United States
GR  - HL-45018/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (EGR1 protein, human)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 9035-58-9 (Thromboplastin)
RN  - EC 3.4.21.5 (Thrombin)
RN  - IT942ZTH98 (Curcumin)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Cells, Cultured
MH  - Curcumin/*pharmacology
MH  - DNA-Binding Proteins/*metabolism
MH  - Early Growth Response Protein 1
MH  - Endothelium, Vascular/drug effects/*metabolism
MH  - Gene Expression
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - *I-kappa B Proteins
MH  - *Immediate-Early Proteins
MH  - Lipopolysaccharides/pharmacology
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*genetics
MH  - Phosphorylation
MH  - RNA, Messenger/genetics
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Thrombin/pharmacology
MH  - Thromboplastin/*genetics
MH  - Transcription Factor AP-1/*metabolism
MH  - Transcription Factors/*metabolism
MH  - Transcription, Genetic
MH  - Transcriptional Activation
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1998/01/23 00:00
MHDA- 1998/01/23 00:01
CRDT- 1998/01/23 00:00
PHST- 1998/01/23 00:00 [pubmed]
PHST- 1998/01/23 00:01 [medline]
PHST- 1998/01/23 00:00 [entrez]
AID - 10.1161/01.atv.17.12.3406 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 1997 Dec;17(12):3406-13. doi: 
      10.1161/01.atv.17.12.3406.