ENDOTHELIN-1 AND THROMBIN SYNERGISTICALLY STIMULATE IL-6 MESSENGER-RNA EXPRESSION AND PROTEIN-PRODUCTION IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS

We investigated the effects of endothelin (ET) and thrombin on the production of interleukin 6 (IL-6) in human umbilical vein endothelial cells (HUVECs). ET-1 increased IL-6 production twofold in HUVECs incubated for 18 h with 10(-10) M ET-1. Thrombin also significantly increased IL-6 production. However, stimulation of HUVECs with ET-1 together with thrombin produced an 18-fold increase in IL-6 production. The ET-1-induced increase was concentration-dependent, with an optimal effect at 100 pM. We then examined the effect of ET-1 on IL-6 mRNA expression in thrombin-stimulated HUVECs. Unstimulated HUVECs spontaneously expressed IL-6 mRNA, which was not modulated by thrombin. Endothelin 1 upregulated IL-6 mRNA expression, with a maximal increase at 100 pM ET-1. These data indicate that the interaction of thrombin and ET-1 induces a synergistic increase in IL-6 production by HUVEC and suggest that ET-1 may therefore play a significant role in inflammation.