Expression of tissue factor pathway inhibitor-2 in murine and human liver regulation during inflammation

Toru Hisaka; Bernard Lardeux; Thierry Lamireau; Torsten Wüestefeld; Patricia F. Lalor; Véronique Neaud; Patrick Maurel; Alexis Desmoulière; Walter Kisiel; Christian Trautwein; Jean Rosenbaum

doi:10.1160/TH03-06-0358

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 91(03): 569-575
DOI: 10.1160/TH03-06-0358

Wound Healing and Inflammation/Infection

Schattauer GmbH

Expression of tissue factor pathway inhibitor-2 in murine and human liver regulation during inflammation

Toru Hisaka

¹GREF, INSERM E 362 and IFR 66, Université Victor Segalen Bordeaux 2, Bordeaux, France

,

Bernard Lardeux

²INSERM U 539, Faculté de Médecine, Nantes, France

,

Thierry Lamireau

¹GREF, INSERM E 362 and IFR 66, Université Victor Segalen Bordeaux 2, Bordeaux, France

,

Torsten Wüestefeld

³Department of Gastroenterology, Hepatology & Endocrinology, Medizinische Hochschule Hannover, Hanover, Germany

,

Patricia F. Lalor

⁴Liver Research Laboratories, University of Birmingham Institute of Clinical Science, Medical Research Council Center for Immune Regulation, Edgbaston, Birmingham, United Kingdom

,

Véronique Neaud

¹GREF, INSERM E 362 and IFR 66, Université Victor Segalen Bordeaux 2, Bordeaux, France

,

Patrick Maurel

⁵INSERM U128, CNRS, Montpellier, France

,

Alexis Desmoulière

¹GREF, INSERM E 362 and IFR 66, Université Victor Segalen Bordeaux 2, Bordeaux, France

,

Walter Kisiel

⁶Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

,

Christian Trautwein

³Department of Gastroenterology, Hepatology & Endocrinology, Medizinische Hochschule Hannover, Hanover, Germany

,

Jean Rosenbaum

¹GREF, INSERM E 362 and IFR 66, Université Victor Segalen Bordeaux 2, Bordeaux, France

› Author Affiliations

Abstract

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Summary

Tissue factor pathway inhibitor-2 (TFPI-2) is a recently described serine proteinase inhibitor. Human and murine TFPI-2 share about 50% homology. The aim of this study was to investigate the cellular localization of human and murine TFPI-2 in the liver and the regulation of their expression during acute inflammation. Northern blot, in situ hybridization and studies on isolated hepatocytes demonstrated a high-level expression of TFPI-2 in murine hepatocytes. On the other hand, very little TFPI-2 mRNA expression could be detected in human liver. Studies with isolated human liver cells suggested that TFPI-2 expression in human liver was mainly observed in liver sinusoidal endothelial cells rather than hepatocytes. Liver murine TFPI-2 expression was greatly increased after lipopolysaccharide administration with a delayed kinetics as compared to α1-acid glycoprotein, a classical acute-phase reactant. Accordingly, studies with isolated cells showed that the increase in TFPI-2 transcripts occurred in non-hepatocytic cells. Moreover, the LPS response was abolished in mice with a hepatocyte-specific KO for the gp130 receptor, thus indicating that a mediator from hepatocytes is involved in the up-regulation of TFPI-2 in non-parenchymal cells. In conclusion, murine TFPI-2 is highly expressed in hepatocytes in the normal murine liver and is upregulated in non-parenchymal cells in the context of inflammation. The large difference in the level of liver expression of human and murine TFPI-2 suggests that despite significant sequence similarities, these proteins presumably have different functions in the two species.

Keywords

Extracellular matrix - inflammatory mediators - proteases/ inhibitors - tissue factor pathway inhibitor (TFPI)

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References

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