TY - JOUR
T1 - Effects of TNF-α and curcumin on the expression of thrombomodulin and endothelial protein C receptor in human endothelial cells
AU - Nan, Bicheng
AU - Lin, Peter
AU - Lumsden, Alan B.
AU - Yao, Qizhi
AU - Chen, Changyi
N1 - Funding Information:
This work is partially supported by research grants from the National Institutes of Health (Chen: R01 HL61943, R01 HL60135, R01 HL65916, R01 HL72716, and R01 EB-002436; Yao: R21 AI 49116 and R01 DE15543; Lumsden: R01 HL75824; and Lin: K08 HL076345).
PY - 2005
Y1 - 2005
N2 - The objective of this study was to elucidate the effects of tumor necrosis factor-alpha (TNF-α) 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-α (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-α (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-α-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-α-treated cells. In addition, EPCR mRNA levels of HUVECs were significantly reduced in TNF-α-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-α on downregulation of TM and EPCR. These data demonstrate that TNF-α significantly decreases expression of TM and EPCR at both mRNA and protein levels in several human endothelial cells. Curcumin can effectively block TNF-α-induced endothelial dysfunction. This study suggests a new molecular mechanism of inflammation-induced thrombosis and a new therapeutic strategy to prevent this clinical problem.
AB - The objective of this study was to elucidate the effects of tumor necrosis factor-alpha (TNF-α) 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-α (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-α (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-α-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-α-treated cells. In addition, EPCR mRNA levels of HUVECs were significantly reduced in TNF-α-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-α on downregulation of TM and EPCR. These data demonstrate that TNF-α significantly decreases expression of TM and EPCR at both mRNA and protein levels in several human endothelial cells. Curcumin can effectively block TNF-α-induced endothelial dysfunction. This study suggests a new molecular mechanism of inflammation-induced thrombosis and a new therapeutic strategy to prevent this clinical problem.
KW - Antioxidant
KW - Curcumin
KW - Endothelial cell
KW - Endothelial protein C receptor
KW - Inflammation
KW - Thrombomodulin
KW - TNF-α
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U2 - 10.1016/j.thromres.2004.10.010
DO - 10.1016/j.thromres.2004.10.010
M3 - Article
C2 - 15733976
AN - SCOPUS:14144250943
SN - 0049-3848
VL - 115
SP - 417
EP - 426
JO - Thrombosis Research
JF - Thrombosis Research
IS - 5
ER -