title: Dengue virus induces thrombomodulin expression in human endothelial cells and monocytes in vitro.
abstract: 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.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Lien-Cheng
authors.initials: LC
authors.lastname: Chen
authors.forename: Huey-Wen
authors.initials: HW
authors.lastname: Shyu
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Lin
authors.forename: Huan-Yao
authors.initials: HY
authors.lastname: Lei
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
authors.forename: Hsiao-Sheng
authors.initials: HS
authors.lastname: Liu
authors.forename: Trai-Ming
authors.initials: TM
authors.lastname: Yeh
mesh_terms: 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
chemical_list: 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