Regulation of Tissue Factor and Thrombomodulin on Cultured Human Dermal Microvascular Endothelial Cells by Herpes Virus Virus Infection

Abstract

Herpes simplex virus(HSV) causes oropharyngeal herpes simplex, genital herpes and keratoconjuntivitis. HSV-infected endothelial cells is a model for vascular injury and possibly the development of atherosclerosis, erythema multiforme, or Beh?et's disease. In this study, we infected cultured human dermal microvascular endothelial cells(HDMEC) with HSV. We then measured coagulation factors associated with fibrinogen accumulation, such as tissue factor and thrombomodulin, in cell lysates and culture supernatants from HSV-1-infected HDMEC to observe whether HSV-1 virus induce a procoagulant activity in cultured HDMEC. Thereafter, we compared the results with those of human umbilical vein endothelial cells(HUVEC). Following the treatment of HSV-1 on cultured HDMEC, the cytopathic effect was observed after 24 hours of incubation and increased until 48 hours of incubation. The expression of tissue factor antigen on HDMEC was induced 4 hours after the treatment of HSV-1. The levels of tissue factor in cell lysates was increased 4 hours after the treatment of HSV-1 to cultured HDMEC and HUVEC, virtually no tissue factor was found in culture supernatants. The maximal levels of tissue factor antigen was found at 16 hours after the treatment of HSV-1 in HDMEC, and 4 hours after the treatment of HSV-1 in HUVEC. The levels of thrombomodulin in cell lysates decreased 4 hours after the treatment of HSV-1 to cultured HDMEC and HUVEC when compared to pretreatment levels. IL-1α and TNFα were observed at 16 hours of incubation after the treatment of HSV-1 on cultured HDMEC. These data suggest that HSV-1 induce a procoagulant activity in both HDMEC and HUVEC. IL-1α or TNFα which is produced by HSV infection may play a role in the induction of tissue factor and reduction of thrombomodulin.