Effects of TNF-alpha and curcumin on the expression of thrombomodulin and endothelial protein C receptor in human endothelial cells

Thromb Res. 2005;115(5):417-26. doi: 10.1016/j.thromres.2004.10.010. Epub 2004 Nov 14.


The objective of this study was to elucidate the effects of tumor necrosis factor-alpha (TNF-alpha) on the expression of thrombomodulin (TM) and endothelial protein C receptor (EPCR) in human endothelial cells as well as the effect of curcumin, a spice and coloring food compound, as a potential therapeutic agent. Human umbilical vein endothelial cells (HUVECs) treated with TNF-alpha (2.0 ng/ml) showed reduced TM mRNA levels by 80%, 97%, 94%, and 97% at 3, 6, 12, and 24 h, respectively (P<0.05), by real-time PCR analysis. Dose-dependent study showed that TM mRNA levels of HUVECs were decreased by 86%, 89%, 91%, and 94% after treatment of TNF-alpha (0, 0.25, 0.5, 1, and 2 ng/ml) for 6 h, respectively (P<0.05). TM protein levels in HUVECs were significantly reduced by 69% in TNF-alpha-treated cells as compared to controls (P<0.05) by Western blot analysis. Secreted protein and activity of TM of HUVEC cultures were also significantly reduced in TNF-alpha-treated cells. In addition, EPCR mRNA levels of HUVECs were significantly reduced in TNF-alpha-treated group as compared to controls (P<0.05). Furthermore, these effects were observed in other types of endothelial cells from human coronary arteries, lung, and skin. Curcumin effectively blocked these effects of TNF-alpha on downregulation of TM and EPCR. These data demonstrate that TNF-alpha significantly decreases expression of TM and EPCR at both mRNA and protein levels in several human endothelial cells. Curcumin can effectively block TNF-alpha-induced endothelial dysfunction. This study suggests a new molecular mechanism of inflammation-induced thrombosis and a new therapeutic strategy to prevent this clinical problem.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Protein C Receptor
  • Gene Expression Regulation / drug effects*
  • Glycoproteins / drug effects
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Humans
  • RNA, Messenger / genetics
  • Receptors, Cell Surface
  • Thrombomodulin / drug effects
  • Thrombomodulin / genetics*
  • Thrombomodulin / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Antigens, CD
  • Endothelial Protein C Receptor
  • Glycoproteins
  • PROCR protein, human
  • RNA, Messenger
  • Receptors, Cell Surface
  • Thrombomodulin
  • Tumor Necrosis Factor-alpha
  • Curcumin