Expression of tissue factor pathway inhibitor-2 in murine and human liver regulation during inflammation.
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 alpha1-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.
Hisaka
Toru
T
GREF, INSERM E 362 and IFR 66, Université Victor Segalen Bordeaux 2, Bordeaux, France.
Lardeux
Bernard
B
Lamireau
Thierry
T
Wüestefeld
Torsten
T
Lalor
Patricia F
PF
Neaud
Véronique
V
Maurel
Patrick
P
Desmoulière
Alexis
A
Kisiel
Walter
W
Trautwein
Christian
C
Rosenbaum
Jean
J
D000210:Acute-Phase Reaction; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015152:Blotting, Northern; D050822:Cytokine Receptor gp130; D010450:Endopeptidases / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D013997:Time Factors; D015854:Up-Regulation
D015703:Antigens, CD; D006023:Glycoproteins; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C021240:tissue-factor-pathway inhibitor 2; D050822:Cytokine Receptor gp130; D010450:Endopeptidases