The dengue virus envelope protein induced PAI-1 gene expression via MEK/ERK pathways

Huey-Wen Shyu; Yi-Ying Lin; Lien-Cheng Chen; Yi-Fen Wang; Trai-Ming Yeh; Shu-Jem Su; Wei-Cheng Cheng; Chang-Yu Chen; Kuan-Hua Lin; Miao-Chen Chou

doi:10.1160/TH10-05-0302

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 104(06): 1219-1227
DOI: 10.1160/TH10-05-0302

Wound Healing and Inflammation / Infection

Schattauer GmbH

The dengue virus envelope protein induced PAI-1 gene expression via MEK/ERK pathways

Authors

Huey-Wen Shyu

¹Department of Medical Technology, Fooyin University, Kaohsiung Hsien, Taiwan
Yi-Ying Lin

¹Department of Medical Technology, Fooyin University, Kaohsiung Hsien, Taiwan

²5th Branch Office, Center for Disease Control, Kaohsiung, Taiwan
Lien-Cheng Chen

³Bureau of Foods and Drug Analysis, Department of Health, Taiwan
Yi-Fen Wang

¹Department of Medical Technology, Fooyin University, Kaohsiung Hsien, Taiwan
Trai-Ming Yeh

⁴Department of Medical Laboratory Sciences and Biotechnology, National Cheng Kung University, Tainan, Taiwan
Shu-Jem Su

¹Department of Medical Technology, Fooyin University, Kaohsiung Hsien, Taiwan
Wei-Cheng Cheng

⁵Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
Chang-Yu Chen

¹Department of Medical Technology, Fooyin University, Kaohsiung Hsien, Taiwan
Kuan-Hua Lin

¹Department of Medical Technology, Fooyin University, Kaohsiung Hsien, Taiwan
Miao-Chen Chou

¹Department of Medical Technology, Fooyin University, Kaohsiung Hsien, Taiwan

Abstract

Summary

Dengue virus (DV) infections cause mild dengue fever or severe life-threatening dengue haemorrhagic fever (DHF)/ dengue shock syndrome (DSS). DV-infected patients have high plasma concentrations of plasminogen activator inhibitor type I (PAI-1). However, the mechanism to cause haemorrhage in DV infections remains poorly understood. In this study, investigation was carried out on the purified recombinant domain III of the envelope glycoprotein of DV serotypes 2 (EIII) and the signalling pathways of EIII leading to PAI-1 gene expression were measured by RT-PCR, Western blot, and immunofluorescence stain. Reporter gene constructs containing serially 5’-deleted sequences of the proximal human PAI-1 promoter region were constructed and then transfected to Huh7 cells, a human hepatoma cell line, prior to EIII treatment. EIII increased the PAI-1 mRNA and protein levels in a dose-dependent manner in Huh7 cells. Results showed that U0126, an inhibitor of extracellular signal-regulated kinase (ERK) kinase (MEK), almost completely suppressed EIII-induced PAI-1 expression. The results suggest that the MEK/ERK signalling pathways mediate the EIII-dependent induction of PAI-1 gene expression via the proximal promoter region.

Keywords

Flaviviridae - dengue virus type 2 - envelope glycoprotein domain III - plasminogen activator inhibitor type-1

Full Text

References

References
1 Gubler DJ. Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century. Trends Microbiol 2002; 10: 100-103.
2 Ahn JD, Morishita R, Kaneda Y. et al. Transcription factor decoy for activator protein-1 (AP-1) inhibits high glucose- and angiotensin II-induced type 1 plasminogen activator inhibitor (PAI-1) gene expression in cultured human vascular smooth muscle cells. Diabetologia 2001; 44: 713-720.
3 Chambers TJ, Liang Y, Droll DA. et al. Yellow fever virus/dengue-2 virus and yellow fever virus/dengue-4 virus chimeras: biological characterization, immunogenicity, and protection against dengue encephalitis in the mouse model. J Virol 2003; 77: 3655-3668.
4 Mukhopadhyay S, Kuhn RJ, Rossmann MG. A structural perspective of the flavivirus life cycle. Nat Rev Microbiol 2005; 3: 13-22.
5 Kuhn RJ, Zhang W, Rossmann MG. et al. Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 2002; 108: 717-725.
6 Preugschat F, Yao CW, Strauss JH. In vitro processing of dengue virus type 2 non-structural proteins NS2A, NS2B, and NS3. J Virol 1990; 64: 4364-4374.
7 Gorbalenya AE, Donchenko AP, Koonin EV. et al. N-terminal domains of putative helicases of flavi- and pestiviruses may be serine proteases. Nucleic Acids Res 1989; 17: 3889-3897.
8 Chambers TJ, Grakoui A, Rice CM. Processing of the yellow fever virus nonstructural polyprotein: a catalytically active NS3 proteinase domain and NS2B are required for cleavages at dibasic sites. J Virol 1991; 65: 6042-6050.
9 Falgout B, Pethel M, Zhang YM. et al. Both nonstructural proteins NS2B and NS3 are required for the proteolytic processing of dengue virus nonstructural proteins. J Virol 1991; 65: 2467-2475.
10 Yon C, Teramoto T, Mueller N. et al. Modulation of the nucleoside triphosphatase/ RNA helicase and 5‘-RNA triphosphatase activities of Dengue virus type 2 non-structural protein 3 (NS3) by interaction with NS5, the RNA-dependent RNA polymerase. J Biol Chem 2005; 280: 27412-27419.
11 Roehrig JT, Bolin RA, Kelly RG. Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus, Jamaica. Virology 1998; 246: 317-328.
12 Crill WD, Roehrig JT. Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are the most efficient blockers of virus adsorption to Vero cells. J Virol 2001; 75: 7769-7773.
13 Rey FA. Dengue virus envelope glycoprotein structure: new insight into its interactions during viral entry. Proc Natl Acad Sci USA 2003; 100: 6899-6901.
14 Roehrig JT. Antigenic structure of flavivirus proteins. Adv Virus Res 2003; 59: 141-175.
15 Mandl CW, Allison SL, Holzmann H. et al. Attenuation of tick-borne encephalitis virus by structure-based site-specific mutagenesis of a putative flavivirus receptor binding site. J Virol 2000; 74: 9601-9609.
16 Hung JJ, Hsieh MT, Young MJ. et al. An external loop region of domain III of dengue virus type 2 envelope protein is involved in serotype-specific binding to mosquito but not mammalian cells. J Virol 2004; 78: 378-388.
17 Chin JF, Chu JJ, Ng ML. The envelope glycoprotein domain III of dengue virus serotypes 1 and 2 inhibit virus entry. Microbes Infect 2007; 9: 1-6.
18 Binder BR, Mihaly J, Prager GW. uPAR-uPA-PAI-1 interactions and signaling: a vascular biologist’s view. Thromb Haemost 2007; 97: 336-342.
19 Vaughan DE. Plasminogen activator inhibitor-1: a common denominator in cardiovascular disease. J Investig Med 1998; 46: 370-376.
20 Hamsten A, Eriksson P. Fibrinolysis and atherosclerosis. Baillieres Clin Haematol 1995; 8: 345-363.
21 Nguyen TH, Lei HY, Nguyen TL. et al. Dengue hemorrhagic fever in infants: a study of clinical and cytokine profiles. J Infect Dis 2004; 189: 221-232.
22 Srikiatkhachorn A. Plasma leakage in dengue haemorrhagic fever. Thromb Haemost 2009; 102: 1042-1049.
23 Roncal C, Orbe J, Belzunce M. et al. The 4G/5G PAI-1 polymorphism influences the endothelial response to IL-1 and the modulatory effect of pravastatin. J Thromb Haemost 2006; 4: 1798-1803.
24 Arndt A, Murphy P, Hart DA. Human HuH-7 hepatoma cells express urokinase and plasminogen activator inhibitor-1: identification, characterization and regulation by inflammatory mediators. Biochim Biophys Acta 1992; 1138: 149-156.
25 de Boer JP, Abbink JJ, Brouwer MC. et al. PAI-1 synthesis in the human hepatoma cell line HepG2 is increased by cytokines--evidence that the liver contributes to acute phase behaviour of PAI-1. Thromb Haemost 1991; 65: 181-185.
26 Madoiwa S, Komatsu N, Mimuro J. et al. Developmental expression of plasminogen activator inhibitor-1 associated with thrombopoietin-dependent megakaryocytic differentiation. Blood 1999; 94: 475-482.
27 Arts J, Grimbergen J, Toet K. et al. On the role of c-Jun in the induction of PAI-1 gene expression by phorbol ester, serum, and IL-1alpha in HepG2 cells. Arterioscler Thromb Vasc Biol 1999; 19: 39-46.
28 Healy AM, Gelehrter TD. Induction of plasminogen activator inhibitor-1 in HepG2 human hepatoma cells by mediators of the acute phase response. J Biol Chem 1994; 269: 19095-19100.
29 Andrew AS, Klei LR, Barchowsky A. AP-1-dependent induction of plasminogen activator inhibitor-1 by nickel does not require reactive oxygen. Am J Physiol Lung Cell Mol Physiol 2001; 281: L616-623.
30 Kutz SM, Higgins CE, Samarakoon R. et al. TGF-beta 1-induced PAI-1 expression is E box/USF-dependent and requires EGFR signaling. Exp Cell Res 2006; 312: 1093-1105.
31 Motojima M, Ando T, Yoshioka T. Sp1-like activity mediates angiotensin-II-induced plasminogen-activator inhibitor type-1 (PAI-1) gene expression in mesangial cells. Biochem J 2000; 349: 435-441.
32 Wong C, Rougier-Chapman EM, Frederick JP. et al. Smad3-Smad4 and AP-1 complexes synergize in transcriptional activation of the c-Jun promoter by transforming growth factor beta. Mol Cell Biol 1999; 19: 1821-1830.
33 Angel P, Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta 1991; 1072: 129-157.
34 Olman MA, Hagood JS, Simmons WL. et al. Fibrin fragment induction of plasminogen activator inhibitor transcription is mediated by activator protein-1 through a highly conserved element. Blood 1999; 94: 2029-2038.
35 Guo B, Inoki K, Isono M. et al. MAPK/AP-1-dependent regulation of PAI-1 gene expression by TGF-beta in rat mesangial cells. Kidney Int 2005; 68: 972-984.
36 Vulin AI, Stanley FM. Oxidative stress activates the plasminogen activator inhibitor type 1 (PAI-1) promoter through an AP-1 response element and cooperates with insulin for additive effects on PAI-1 transcription. J Biol Chem 2004; 279: 25172-25178.
37 Lin JL, Chen HC, Fang HI. et al. MST4, a new Ste20-related kinase that mediates cell growth and transformation via modulating ERK pathway. Oncogene 2001; 20: 6559-6569.
38 Chen LC, Yeh TM, Lin YY. et al. The envelope glycoprotein domain III of dengue virus type 2 induced the expression of anticoagulant molecules in endothelial cells. Mol Cell Biochem. 2010
39 el-Roeiy A, Dmowski WP, Gleicher N. et al. Danazol but not gonadotropin-releasing hormone agonists suppresses autoantibodies in endometriosis. Fertil Steril 1988; 50: 864-871.
40 Shyu HW, Hsu SH, Hsieh-Li HM. et al. Forced expression of RNF36 induces cell apoptosis. Exp Cell Res 2003; 287: 301-313.
41 Loskutoff DJ, Sawdey M, Keeton M. et al. Regulation of PAI-1 gene expression in vivo. Thromb Haemost 1993; 70: 135-137.
42 Wills BA, Oragui EE, Stephens AC. et al. Coagulation abnormalities in dengue hemorrhagic Fever: serial investigations in 167 Vietnamese children with Dengue shock syndrome. Clin Infect Dis 2002; 35: 277-285.
43 Van Gorp EC, Setiati TE, Mairuhu AT. et al. Impaired fibrinolysis in the pathogenesis of dengue hemorrhagic fever. J Med Virol 2002; 67: 549-554.
44 Hageman J, Eggen BJ, Rozema T. et al. Radiation and transforming growth factor-beta cooperate in transcriptional activation of the profibrotic plasminogen activator inhibitor-1 gene. Clin Cancer Res 2005; 11: 5956-5964.
45 Sakamoto T, Woodcock-Mitchell J, Marutsuka K. et al. TNF-alpha and insulin, alone and synergistically, induce plasminogen activator inhibitor-1 expression in adipocytes. Am J Physiol 1999; 276: C1391-1397.
46 Descheemaeker KA, Wyns S, Nelles L. et al. Interaction of AP-1-, AP-2-, and Sp1-like proteins with two distinct sites in the upstream regulatory region of the plasminogen activator inhibitor-1 gene mediates the phorbol 12-myristate 13-acetate response. J Biol Chem 1992; 267: 15086-15091.
47 Arts J, Grimbergen J, Bosma PJ. et al. Role of c-Jun and proximal phorbol 12-myristate-13-acetate-(PMA)-responsive elements in the regulation of basal and PMA-stimulated plasminogen-activator inhibitor-1 gene expression in HepG2. Eur J Biochem 1996; 241: 393-402.
48 Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature 2001; 410: 37-40.
49 Perfettini JL, Castedo M, Roumier T. et al. Mechanisms of apoptosis induction by the HIV-1 envelope. Cell Death Differ 2005; 12 (Suppl. 01) 916-923.
50 Pasten C, Olave NC, Zhou L. et al. Polyphenols downregulate PAI-1 gene expression in cultured human coronary artery endothelial cells: molecular contributor to cardiovascular protection. Thromb Res 2007; 121: 59-65.
51 Hasan RN, Schafer AI. Hemin upregulates Egr-1 expression in vascular smooth muscle cells via reactive oxygen species ERK-1/2-Elk-1 and NF-kappaB. Circ Res 2008; 102: 42-50.
52 Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 1997; 9: 180-186.
53 van Gorp EC, Suharti C, ten Cate H. et al. Review: infectious diseases and coagulation disorders. J Infect Dis 1999; 180: 176-186.
54 Sosothikul D, Seksarn P, Pongsewalak S. et al. Activation of endothelial cells, coagulation and fibrinolysis in children with Dengue virus infection. Thromb Haemost 2007; 97: 627-634.
55 Huerta-Zepeda A, Cabello-Gutierrez C, Cime-Castillo J. et al. Crosstalk between coagulation and inflammation during Dengue virus infection. Thromb Haemost 2008; 99: 936-943.
56 Suharti C, van Gorp EC, Setiati TE. et al. The role of cytokines in activation of coagulation and fibrinolysis in dengue shock syndrome. Thromb Haemost 2002; 87: 42-46.
57 Schnittler HJ, Feldmann H. Viral hemorrhagic fever--a vascular disease?. Thromb Haemost 2003; 89: 967-972.
58 Huang YH, Lei HY, Liu HS. et al. Tissue plasminogen activator induced by dengue virus infection of human endothelial cells. J Med Virol 2003; 70: 610-616.
59 Cabello-Gutierrez C, Manjarrez-Zavala ME, Huerta-Zepeda A. et al. Modification of the cytoprotective protein C pathway during Dengue virus infection of human endothelial vascular cells. Thromb Haemost 2009; 101: 916-928.
60 Dimova EY, Kietzmann T. Metabolic, hormonal and environmental regulation of plasminogen activator inhibitor-1 (PAI-1) expression: lessons from the liver. Thromb Haemost 2008; 100: 992-1006.
61 Dai J, Huang C, Wu J. et al. Iron-induced interleukin-6 gene expression: possible mediation through the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways. Toxicology 2004; 203: 199-209.
62 Roger T, Bresser P, Snoek M. et al. Exaggerated IL-8 and IL-6 responses to TNF-alpha by parainfluenza virus type 4-infected NCI-H292 cells. Am J Physiol Lung Cell Mol Physiol 2004; 287: L1048-1055.
63 Dragon S, Rahman MS, Yang J. et al. IL-17 enhances IL-1beta-mediated CXCL-8 release from human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2007; 292: L1023-1029.
64 Sadowska B, Barrucco R, Khalili K. et al. Regulation of human polyomavirus JC virus gene transcription by AP-1 in glial cells. J Virol 2003; 77: 665-672.
65 Kohno M, Pouyssegur J. Pharmacological inhibitors of the ERK signaling pathway: application as anticancer drugs. Prog Cell Cycle Res 2003; 5: 219-224.
66 Medin CL, Rothman AL. Cell type-specific mechanisms of interleukin-8 induction by dengue virus and differential response to drug treatment. J Infect Dis 2006; 193: 1070-1077.
67 Matsuda T, Almasan A, Tomita M. et al. Dengue virus-induced apoptosis in hepatic cells is partly mediated by Apo2 ligand/tumour necrosis factor-related apoptosis-inducing ligand. J Gen Virol 2005; 86: 1055-1065.
68 Monroy V, Ruiz BH. Participation of the Dengue virus in the fibrinolytic process. Virus Genes 2000; 21: 197-208.