Endothelial Cell Protein S Synthesis Is Upregulated by the Complex of IL-6 and Soluble IL-6 Receptor

W Craig Hooper; Donald J Phillips; Bruce L Evatt

doi:10.1055/s-0038-1656095

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1997; 77(05): 1014-1019
DOI: 10.1055/s-0038-1656095

Vessel Wall

Schattauer GmbH Stuttgart

Endothelial Cell Protein S Synthesis Is Upregulated by the Complex of IL-6 and Soluble IL-6 Receptor

W Craig Hooper

The Division of HIV/AIDS, Hematologic Diseases Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, USA

,

Donald J Phillips

The Division of HIV/AIDS, Hematologic Diseases Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, USA

,

Bruce L Evatt

The Division of HIV/AIDS, Hematologic Diseases Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, USA

› Author Affiliations

Abstract

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Summary

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, gpl30. Neutralizing antibodies directed against either IL-6 or gpl30 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 gpl30 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.

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References

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