Cytokine regulation of hemostatic property and IL-6 production of human endothelial cells.
The effects of four inflammatory cytokines, IL-1, TNF, IFN-gamma, and IL-6, were assessed on the following functions of human vascular endothelial cells (EC) in culture: expression of procoagulant activity (PCA), endothelial cell-associated thrombomodulin (TM), and IL-6 production. Both IL-1 and TNF induced PCA, reduced TM, and induced IL-6 production in a dose-dependent manner. IFN-gamma had a weak but significant reducing effect on TM and an inducing effect on IL-6 production, while it had no effect on PCA expression. IFN-gamma, however, when added in combination with either IL-1 or TNF, modulated the effects of these cytokines; INF-gamma inhibited the PCA expression and enhanced the reduction of TM and the production of IL-6, which were induced by either IL-1 or TNF. In contrast, IL-6 had no significant effect on the EC functions studied. These results suggest that both IL-1 and TNF are the major cytokines affecting the EC functions that determine the association between the coagulation and the inflammatory response, and that IFN-gamma affects this phenomenon predominantly through the modification of the effects of these cytokines.
Hashimoto
Y
Y
Department of Medicine & Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Hirohata
S
S
Kashiwado
T
T
Itoh
K
K
Ishii
H
H
D001780:Blood Coagulation Tests; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000032:analysis; D018179:Receptors, Thrombin; D013917:Thrombin
D016207:Cytokines; D015850:Interleukin-6; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D013917:Thrombin