Tissue plasminogen activator induced by dengue virus infection of human endothelial cells.
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.
Huang
Ying-Huey
YH
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Lei
Huan-Yao
HY
Liu
Hsiao-Sheng
HS
Lin
Yee-Shin
YS
Chen
Shun-Hua
SH
Liu
Ching-Chuan
CC
Yeh
Trai-Ming
TM
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
D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D010959:Tissue Plasminogen Activator