Dengue virus induces thrombomodulin expression in human endothelial cells and monocytes in vitro.
OBJECTIVE
Dengue virus (DV) infections can cause severe life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). However, the mechanism to cause hemorrhage in DV infections remains poorly understood. Thrombomodulin (TM), expressed on the surface of endothelial cells and monocytes, is very important in regulation of coagulation and inflammation. Therefore, the effect of DV on the TM expression was studied in vitro using both endothelial cells and monocytes.


RESULTS
The expression of TM in human endothelial cell line, HMEC-1, monocytic cell line THP-1 and peripheral blood mononuclear cells derived from human blood was increased after DV infection, UV-inactivated DV or recombinant DV envelop protein domain III stimulation as demonstrated by flow cytometry and immunofluorescent staining. Western blot analysis further confirmed only DV but not enterovirus 71 infection of HMEC-1 cells increased TM protein expression. In addition, RT-PCR analysis showed the increase of TM mRNA as well as other protein C activation-related molecules in DV stimulated HMEC-1 in a dose-dependent manner.


CONCLUSIONS
These results suggest that DV stimulation of human endothelial cells and monocytes can increase the expression of TM, which may contribute to the anticoagulant properties of cells during DV infection.
Chen
Lien-Cheng
LC
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan, ROC.
Shyu
Huey-Wen
HW
Lin
Hui-Min
HM
Lei
Huan-Yao
HY
Lin
Yee-Shin
YS
Liu
Hsiao-Sheng
HS
Yeh
Trai-Ming
TM
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D003716:Dengue Virus / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism* / Q000821:virology; D000074283:Endothelial Protein C Receptor; D029821:Enterovirus A, Human / Q000502:physiology; D004769:Enterovirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D006801:Humans; D009000:Monocytes / Q000378:metabolism* / Q000821:virology; D017293:Protein S / Q000096:biosynthesis / Q000235:genetics; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D019595:Severe Dengue / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D018180:Thrombomodulin / Q000096:biosynthesis* / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics; D015533:Transcriptional Activation; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000737:chemistry
D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D017293:Protein S; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D018180:Thrombomodulin; D014759:Viral Envelope Proteins; C072281:E protein TH Sman, Dengue virus; C083866:T103N, KHRR 296-299 AAAA; D010959:Tissue Plasminogen Activator