UP-REGULATION OF THROMBOMODULIN BY ACTIVATION OF HISTAMINE H-1-RECEPTORS IN HUMAN UMBILICAL-VEIN ENDOTHELIAL-CELLS INVITRO

被引:28
作者
HIROKAWA, K [1 ]
AOKI, N [1 ]
机构
[1] TOKYO MED & DENT UNIV,DEPT MED 1,YUSHIMA,BUNKYO KU,TOKYO 113,JAPAN
关键词
D O I
10.1042/bj2760739
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous reports demonstrated that the expression of thrombomodulin (TM) in endothelial cells was modulated by various agents. Although TM was down-regulated by endotoxin or cytokines, up-regulation of TM was accomplished when endothelial cells were stimulated with unphysiologically high concentrations of cyclic AMP derivatives or tumour-promoting phorbol esters. We investigated the expression of TM in human umbilical-vein endothelial cells (HUVECs) by physiological substances that can be released into the bloodstream. Histamine (0.1-10-mu-M, 1-48 h) increased TM activity, TM antigen in cell lysates and TM mRNA levels, but 5-hydroxytryptamine and bradykinin had no effect. Enhancement of TM activity by histamine was completely blocked by the H-1-selective antagonist pyrilamine, whereas the H-2-antagonist cimetidine had no effect, showing that histamine up-regulates TM activity via H-1-receptors on HUVECs. Enhanced TM activity by histamine and the resultant increase in protein C activation might play a role in a feedback regulation for prevention of vascular thrombosis.
引用
收藏
页码:739 / 743
页数:5
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