Endothelial cell protein S synthesis is upregulated by the complex of IL-6 and soluble IL-6 receptor

• Published in: Thrombosis and haemostasis Vol. 77; no. 5; p. 1014
• Main Authors: Hooper, W C, Phillips, D J, Evatt, B L
• Format: Journal Article
• Language: English
• Published: Germany 01.05.1997
• Subjects: Antigens, CD - physiology; Cells, Cultured; Cytokines - pharmacology; Dexamethasone - pharmacology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Gene Expression - drug effects; Growth Inhibitors - pharmacology; Humans; Interleukin-1 - pharmacology; Interleukin-11 - pharmacology; Interleukin-6 - pharmacology; Kinetics; Leukemia Inhibitory Factor; Lymphokines - pharmacology; Oncostatin M; Peptides - pharmacology; Protein S - biosynthesis; Receptors, Interleukin - physiology; Receptors, Interleukin-6; Recombinant Proteins - pharmacology; Tumor Necrosis Factor-alpha - pharmacology; Umbilical Veins
• ISSN: 0340-6245
• DOI: 10.1055/s-0038-1656095

We have recently demonstrated that the proinflammatory cytokine, interleukin-6 (IL-6), could upregulate the production of protein S in the human hepatoma cell line, HepG-2, but not in endothelial cells. In this study, we have demonstrated that the combination of exogenous IL-6 and soluble IL-6 receptor (sIL-6R) could significantly upregulate protein S production in both primary human umbilical vein endothelial cells (HUVEC) and in the immortalized human microvascular endothelial cell line, HMEC-1. The IL-6/sIL-6R complex was also able to rapidly induce tyrosine phosphorylation of the IL-6 transducer, gp130. Neutralizing antibodies directed against either IL-6 or gp130 blocked protein S upregulation by the IL-6/sIL-6R complex. It was also observed that exogenous sIL-6R could also upregulate protein S by forming a complex with IL-6 constitutively produced by the endothelial cell. Two other cytokines which also utilize the gp130 receptor, oncostatin M (OSM) and leukemia inhibitory factor (LIF), were also able to upregulate endothelial cell protein S. This study demonstrates a mechanism that allows endothelial cells to respond to IL-6 and also illustrates the potential importance of circulating soluble receptors in the regulation of the anticoagulation pathway.