title: Tissue plasminogen activator induced by dengue virus infection of human endothelial cells.
abstract: Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are severe complications of dengue virus (DV) infection. However, the pathogenesis of hemorrhage induced by dengue virus infection is poorly understood. Since endothelial cells play a pivotal role in the regulation of hemostasis, we studied the effect of DV infection on the production of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) in vitro using both primary isolated endothelial cells, human umbilical cord veins cells, and a human microvascular endothelial cell line. DV infection significantly induced the secretion of tPA but not PAI-1 of human endothelial cells. In addition, tPA mRNA of endothelial cells was induced by DV as demonstrated by RT-PCR. Antibody against IL-6 but not control antibody inhibited DV-induced tPA production of endothelial cells. Furthermore, a good correlation between sera levels of IL-6 and tPA was found in DHF but not DF patients. These results suggest that IL-6 can regulate DV-induced tPA production of endothelial cells, which may play important roles in the pathogenic development of DHF/DSS.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Ying-Huey
authors.initials: YH
authors.lastname: Huang
authors.forename: Huan-Yao
authors.initials: HY
authors.lastname: Lei
authors.forename: Hsiao-Sheng
authors.initials: HS
authors.lastname: Liu
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
authors.forename: Shun-Hua
authors.initials: SH
authors.lastname: Chen
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Liu
authors.forename: Trai-Ming
authors.initials: TM
authors.lastname: Yeh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003716:Dengue Virus / Q000472:pathogenicity*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019595:Severe Dengue / Q000378:metabolism* / Q000821:virology; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014471:Umbilical Veins
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D010959:Tissue Plasminogen Activator