Inhibition of lipopolysaccharide-induced tissue factor expression in monocytes by urinary trypsin inhibitor in vitro and in vivo

Perenlei Molor-Erdene; Kenji Okajima; Hirotaka Isobe; Mitsuhiro Uchiba; Naoaki Harada; Nobuhiko Shimozawa; Hiroaki Okabe

doi:10.1160/TH04-09-0577

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(01): 136-145
DOI: 10.1160/TH04-09-0577

Platelets and Blood Cells

Schattauer GmbH

Inhibition of lipopolysaccharide-induced tissue factor expression in monocytes by urinary trypsin inhibitor in vitro and in vivo

Perenlei Molor-Erdene

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Kenji Okajima

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Hirotaka Isobe

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Mitsuhiro Uchiba

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Naoaki Harada

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Nobuhiko Shimozawa

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Hiroaki Okabe

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

› Author Affiliations

Abstract

Summary

Tissue factor (TF) plays a critical role in the pathogenesis of disseminated intravascular coagulation (DIC) observed in patients with septic shock. Urinary trypsin inhibitor (UTI), a multivalent protease inhibitor, is currently used for treatment of patients with septic shock. This study was undertaken to determine whether UTI reduces LPS-induced coagulation abnormalities by inhibiting lipopolysaccharide (LPS)-induced expression of TF by monocytes. UTI inhibited LPS-induced increases in both TF activities andTF mRNA expression in monocytes without affecting the viability. Although activation of nuclear factor-κB (NF-κB), activator protein-1 (AP-1) and extracellular signal-regulated kinase (ERK)1/2 were shown to be critically involved in LPS-induced increases in TF activities in isolated monocytes, UTI inhibited phosphorylation of ERK1/2 and decreased expression of early growth response factor-1 (Egr-1) induced by LPS without affecting the activation of NF-κB and AP-1. UTI inhibited both the expression of TF mRNA in whole blood, increases in TF activities in mononuclear cells, and increases in serum levels of fibrin and fibrinogen degradation products (E) in rats given LPS without affecting the number of monocytes in the peripheral blood. Taken together these results strongly suggested that UTI might reduce LPS-induced coagulation abnormalities in rats by inhibiting TF expression in monocytes through inhibition of Egr-1 expression.

Keywords

Tissue factor - monocytes - Egr-1 - disseminated intravascular coagulation

Full Text

References

References
1 Levi M, de Jonge E, van der Poll T. et al. Disseminated intravascular coagulation. Thromb Haemost 1999; 82: 695-705.
2 Camerer E, Kolsto AB, Prydz H. Cell biology of tissue factor, the principal initiator of blood coagulation. Thromb Res 1996; 81: 1-41.
3 ten Cate H. Pathophysiology of disseminated intravascular coagulation in sepsis. Crit Care Med 2000; 28: S9-S11.
4 Østerud B. Tissue factor expression by monocytes: regulation and pathophysiological roles. Blood Coagul Fibrinolysis 1998; 9: S9-S14.
5 Mackman N. Regulation of tissue factor gene. Thromb Haemost 1997; 78: 747-54.
6 Oeth P, Parry GC, Mackman N. Regulation of tissue factor gene in human monocytic cells. Role of AP-1, NF-κB/Rel, and Sp1 proteins in uninduced and lipopolysaccharide-induced expression. Arterioscler Thromb Vasc Biol 1997; 17: 365-74.
7 Mackman N, Brand K, Edgington TS. Lipopolysaccharide- mediated transcriptional activation of the human tissue factor gene in THP-1 monocytic cells requires both activator protein 1 and nuclear factor-κB binding sites. J Exp Med 1991; 174: 1517-26.
8 Groupp ER, Donovan-Peluso M. Lipopolysaccharide induction of THP-1 cells activates binding of c-Jun, Ets, and Egr-1 to the tissue factor promoter. J Biol Chem 1996; 271: 12423-30.
9 Baldwin Jr AS. The NF-κB and IκB proteins: new discoveries and insights. Annu Rev Immunol 1996; 14: 649-83.
10 Whitmarsh AJ, Davis RJ. Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J M Med 1996; 74: 589-607.
11 Hall AJ, Vos HL, Bertina RM. Lipopolysaccharide induction of tissue factor in THP-1 cells involves Jun protein phosphorylation and nuclear factor-κB nuclear translocation. J Biol Chem 1999; 274: 376-83.
12 Chu AJ, Wang ZG, Walton MA. et al. Involvement of MAPK activation in bacterial endotoxin-inducible tissue factor upregulation in human monocytic THP-1 cells. J Surg Res 2001; 101: 85-90.
13 Sukhatme VP. Early transcriptional events in cell growth: the Egr family. J Am Soc Nephrol 1990; 1: 859-66.
14 Guha M, O'Connell MA, Pawlinski R. et al. Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor α expression by inducing Elk-1 phosphorylation and Egr-1 expression. Blood 2001; 98: 1429-39.
15 Jönsson BM, Ohlsson K, Rosengren M. Radioimmunological quantitation of the urinary trypsin inhibitor in normal blood and urine. Biol Chem 1989; 370: 1157-61.
16 Hirose J, Ozawa T, Miura T. et al. Human neutrophil elastase degrades inter-alpha-trypsin inhibitor to liberate urinary trypsin inhibitor related proteins. Biol Pharm Bull 1998; 21: 651-6.
17 Nishiyama T, Aibiki M, Hanaoka K. The effects of ulinastatin, a human protease inhibitor, on the transfusion- induced increase of plasma polyMphonuclear granulocyte elastase. Anesth Analg 1996; 82: 108-12.
18 Okabe H, Irita K, Kurosawa K. et al. Increase in the plasma concentration of reduced glutathione observed in rats with liver damage induced by lipopolysaccharide/ D-galactosamine: effects of ulinastatin, a urinary trypsin inhibitor. Circ Shock 1993; 41: 268-72.
19 Ohnishi H, Kosuzume H, Ashida Y. et al. Effects of urinary trypsin inhibitor on pancreatic enzymes and experimental acute pancreatitis. Digest Dis Sci 1984; 29: 26-32.
20 Kobayashi H, Suzuki M, Tanaka Y. et al. Suppression of urokinase expression and invasiveness by urinary trypsin inhibitor is mediated through inhibition of protein kinase C-and MEK/ERK/c-Jun-dependent signaling pathways. J Biol Chem 2001; 276: 2015-22.
21 Morishita H, Yamakawa T, Matsusue T. et al. Novel factor Xa and plasma kallikrein inhibitory-activities of the second Kunits type inhibitory domain of urinary trypsin inhibitor. Thromb Res 1994; 73: 193-204.
22 Uchiba M, Okajima K, Murakami K. et al. Effect of nafamostat mesilate on pulmonary vascular injury induced by lipopolysaccharide in rats. Am J Respir Crit Care Med 1997; 155: 711-8.
23 Mechtcheriakova D, Wlachos A, Holzmuller H. et al. Vascular endothelial cell growth factor-induced tissue factor expression in endothelial cells is mediated by EGR-1. Blood 1999; 93: 3811-23.
24 Yuksel M, Okajima K, Uchiba M. et al. Gabexate mesilate, a synthetic protease inhibitor, inhibits lipopolysaccharide- induced tumor necrosis factor-α?production by inhibiting activation of both nuclear factor- κB and activator protein-1 in human monocytes. J Pharmacol Exp Ther 2003; 305: 298-305.
25 Shen Z, Peedikayil J, Olson GK. et al. Multiple transcription factor profiling by enzyme-linked immunoassay. Biotechniques 2002; 32: 1168-77.
26 Sato Y, Ishikawa S, Otaki A. et al. Induction of acute-phase reactive substances during open-heart surgery and efficacy of ulinastatin. Inhibiting cytokines and postoperative organ injury. Jpn J Thorac Cardiovasc Surg 2000; 48: 428-34.
27 Ohzawa N, Takahashi Y, Tsuchiya T. et al. Study on the metabolic fate of ulinastatin (1): pharmacokinetics in rats, mice and rabbits following a single intravenous dose. Yakubutudoutai 1990; 5: 739-53. (Abstract in English)
28 Uchiba M, Okajima K, Murakami K. et al. rhs-TM prevents ET-induced increase in pulmonary vascular permeability through protein C activation. Am J Physiol 1997; 273: L889-94.
29 Uchiba M, Okajima K, Murakami K. et al. Attenuation of endotoxin-induced pulmonary vascular injury by antithrombin III. Am J Physiol 1996; 270: L921-30.
30 Nakamura S, Imamura T, Okamoto K. Tissue factor in neutrophils: yes. J Thromb Haemost 2004; 2: 214-7.
31 Ruan QR, Zhang WJ, Hufnagl P. et al. Anisodamine counteracts lipopolysaccharide-induced tissue factor and plasminogen activator inhibitor-1 expression in human endothelial cells: contribution of the NF-κB pathway. J Vasc Res 2001; 38: 13-9.
32 Pawlinski R, Pedersen B, Schabbauer G. et al. Role of tissue factor and protease activated receptors in a mouse model of endotoxemia. Blood 2004; 103: 1342-7.
33 Slota A, Sjoquist M, Wolgast M. et al. Bikunin in rat plasma, lymph and bile. Biol Chem Hoppe Seyler 1994; 375: 127-33.
34 Aosasa S, Ono S, Mochizuki H. et al. Mechanism of the inhibitory effect of protease inhibitor on tumor necrosis factor α production of monocytes. Shock 2001; 15: 101-5.
35 Voigtlander C, Rand A, Liu SL. et al. Suppression of tissue factor expression, cofactor activity, and metastatic potential of murine melanoma cells by the N-terminal domain of adenovirus E1A 12S protein. J Cell Biochem 2002; 85: 54-71.
36 Guha M, Mackman N. The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. J Biol Chem 2002; 277: 32124-32.
37 Yao J, Mackman N, Edgington TS. et al. Lipopolysaccharied induction of the tumor necrosis factor-α promoter in human monocytic cells; regulation by Egr-1, c-Jun and NF-κB transcription factors. J Biol Chem 1997; 272: 17795-801.
38 Naworth PP, Stern DM. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 1986; 163: 740-5.
39 Moore KL, Esmon CT, Esmon NL. Tumor necrosis factor leads to the internalization and degradation of thrombomodulin from the surface of bovine aortic endothelial cells in culture. Blood 1989; 73: 159-65.
40 Kobayashi M, Shimada K, Ozawa T. Human recombinant interleukin-1β-and tumor necrosis factor-α-mediated suppression of heparin like compounds on cultured porcine aortic endothelial cells. J Cell Physiol 1990; 144: 383-90.
41 Mimura K, Shinozawa K, Kobayashi T. et al. Inhibitory effect of ulinastatin on the alpha-thrombin activation of factors V and VIII. Rinsho Byori. 1992; 40: 317-20 (Abstract in English)
42 Blom AM, Morgelin M, Oyen M. et al. Structural characterization of inter-α-inhibitor. Evidence for an extended shape. J Biol Chem 1999; 274: 298-304.
43 Ødum L. Inter-α-trypsin inhibitor and pre-α-trypsin inhibitor in health and disease. Determination by immuno-electrophoresis and immunoblotting. Biol Chem Hoppe Seyler 1990; 371: 1153-8.
44 Jourdain M, Carrette O, Tournoys A. et al. Effects of inter-α-inhibitor in experimental endotoxic shock and disseminated intravascular coagulation. Am J Respir Crit Care Med 1997; 156: 1825-33.
45 Taylor FB, Chang A, Ruf W. et al. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ shock 1991; 33: 127-34.
46 Riewald M, Ruf W. Orchestration of coagulation protease signaling by tissue factor. Trends Cardiovasc Med. 2002; 12: 149-54.