ET-1 induces IL-6 gene expression in human umbilical vein endothelial cells: synergistic effect of IL-1.
Endothelins are a family of potent vasoactive peptides that have also been implicated in inflammation. To examine the consequence of endothelin stimulation on cytokine production, we explored the effect of endothelin-1 (ET-1) on interleukin-6 (IL-6) gene expression. ET-1 augmented the production of IL-6 in human umbilical vein endothelial cells (HUVEC) by 2- to 5-fold and synergized with IL-1 to induce a 150-fold increase in IL-6 secretion, compared with spontaneous production. The peak of IL-6 production was in the presence of 100 pM ET-1 after 12 h of stimulation. ET-1 augmented IL-6 mRNA expression at the optimal concentration of 100 pM, in the presence of 1 ng/ml of IL-1. ET-1-induced IL-6 mRNA expression was significant within 4 h of stimulation and persisted for 18 h. Similarly, the ETB receptor-specific agonist, IRL-1620, also augmented IL-6 mRNA expression and IL-6 protein production in HUVEC. Our results suggest that endothelin may play a role at the vascular inflammatory site by modulating cytokine production through ETB receptor activation in endothelial cells of human origin.
Stankova
J
J
Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
D'Orléans-Juste
P
P
Rola-Pleszczynski
M
M
D002478:Cells, Cultured; D004357:Drug Synergism; D019332:Endothelin-1 / Q000008:administration & dosage*; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000235:genetics*; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists; D014471:Umbilical Veins
D019332:Endothelin-1; D016232:Endothelins; D007375:Interleukin-1; D015850:Interleukin-6; D010446:Peptide Fragments; D012333:RNA, Messenger; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C074308:sovateltide