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.
Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
J
J
Stankova
P
P
D'Orléans-Juste
M
M
Rola-Pleszczynski
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