IL-6 Upregulates Protein S Expression in the HepG-2 Hepatoma Cells

W Craig Hooper; Donald J Phillips; Maria Ribeiro; Jane Benson; Bruce L Evatt

doi:10.1055/s-0038-1653874

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1995; 73(05): 819-824
DOI: 10.1055/s-0038-1653874

Original Articles

Coagulation

Schattauer GmbH Stuttgart

IL-6 Upregulates Protein S Expression in the HepG-2 Hepatoma Cells

Authors

W Craig Hooper

The Division of HIV/AIDS, Htematologic Diseases Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
Donald J Phillips

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

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

The Division of HIV/AIDS, Htematologic Diseases Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
Bruce L Evatt

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

Abstract

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Summary

Several pro-inflammatory cytokines have been shown to be important in the modulation of the procoagulant response. However, what role these cytokines may have in the regulation of coagulation inhibitors is poorly understood. While the hepatocyte is a primary site of synthesis for the anticoagulant proteins C and S, it is also a major target cell for the proinflammatory cytokine, IL-6. We have found that stimulation of HepG-2 hepatoma cells with IL-6 (5 ng/ml) significantly increased the production of the anticoagulant cofactor, protein S, in both a time and dose dependent fashion. This increase was seen at both the RNA and protein level. A mouse monoclonal neutralizing antibody to human IL-6 suppressed the IL-6 effect in a concentration dependent fashion. IL-6 also increased the release of the C4b-binding protein but had no effect on protein C production. When combined with either dexamethasone or soluble IL-6 receptor, the IL-6 response was significantly enhanced. Oncostatin M, a functionally related cytokine, had a similar effect while other related cytokines, IL-11 and leukemia inhibitory factor, only had a marginal effect. IL-1, TGF-β, and TNF-α had no significant effect on protein S production. These results indicate that IL-6 may play an important regulatory role in the anticoagulant pathway.

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References

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