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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
1   GREF, INSERM E 362 and IFR 66, Université Victor Segalen Bordeaux 2, Bordeaux, France
,
Bernard Lardeux
2   INSERM U 539, Faculté de Médecine, Nantes, France
,
Thierry Lamireau
1   GREF, INSERM E 362 and IFR 66, Université Victor Segalen Bordeaux 2, Bordeaux, France
,
Torsten Wüestefeld
3   Department of Gastroenterology, Hepatology & Endocrinology, Medizinische Hochschule Hannover, Hanover, Germany
,
Patricia F. Lalor
4   Liver Research Laboratories, University of Birmingham Institute of Clinical Science, Medical Research Council Center for Immune Regulation, Edgbaston, Birmingham, United Kingdom
,
Véronique Neaud
1   GREF, INSERM E 362 and IFR 66, Université Victor Segalen Bordeaux 2, Bordeaux, France
,
Patrick Maurel
5   INSERM U128, CNRS, Montpellier, France
,
Alexis Desmoulière
1   GREF, INSERM E 362 and IFR 66, Université Victor Segalen Bordeaux 2, Bordeaux, France
,
Walter Kisiel
6   Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
,
Christian Trautwein
3   Department of Gastroenterology, Hepatology & Endocrinology, Medizinische Hochschule Hannover, Hanover, Germany
,
Jean Rosenbaum
1   GREF, INSERM E 362 and IFR 66, Université Victor Segalen Bordeaux 2, Bordeaux, France
› Author AffiliationsFinancial support: This work was supported by grants from Comité de la Dordogne from the Ligue Nationale Contre le Cancer, Association pour la Recherche sur la Cancer, and Conseil Régional d’Aquitaine. WK was supported by a grant (HL-64119) from the National Institutes of Health.
Further Information

Publication History

Received 12 June 2003

Accepted after resubmission 23 February 2003

Publication Date:
05 December 2017 (online)

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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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