15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits Tissue Factor Expression in Human Macrophages and Endothelial Cells: Evidence for ERK1/2 Signaling Pathway Blockade

S. Eligini; C. Banfi; M. Brambilla; M. Camera; S. S. Barbieri; F. Poma; E. Tremoli; S. Colli

doi:10.1055/s-0037-1613247

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2002; 88(03): 524-532
DOI: 10.1055/s-0037-1613247

Review Article

Schattauer GmbH

15-Deoxy-Δ^12,14-Prostaglandin J₂ Inhibits Tissue Factor Expression in Human Macrophages and Endothelial Cells: Evidence for ERK1/2 Signaling Pathway Blockade

S. Eligini

¹E. Grossi Paoletti Center, Department of Pharmacological Sciences, University of Milan, Milan, Italy

,

C. Banfi

¹E. Grossi Paoletti Center, Department of Pharmacological Sciences, University of Milan, Milan, Italy

,

M. Brambilla

¹E. Grossi Paoletti Center, Department of Pharmacological Sciences, University of Milan, Milan, Italy

,

M. Camera

¹E. Grossi Paoletti Center, Department of Pharmacological Sciences, University of Milan, Milan, Italy

,

S. S. Barbieri

¹E. Grossi Paoletti Center, Department of Pharmacological Sciences, University of Milan, Milan, Italy

,

F. Poma

¹E. Grossi Paoletti Center, Department of Pharmacological Sciences, University of Milan, Milan, Italy

,

E. Tremoli

¹E. Grossi Paoletti Center, Department of Pharmacological Sciences, University of Milan, Milan, Italy

,

S. Colli

¹E. Grossi Paoletti Center, Department of Pharmacological Sciences, University of Milan, Milan, Italy

› Institutsangaben

Abstract

Summary

Basic and clinical evidence has provided insight into the molecular events that link inflammation and coagulation. Increased expression of tissue factor (TF) by circulating and vascular cells has been indicated as responsible for the thrombotic complications associated with acute and chronic inflammation. TF is indeed inducible in circulating and vascular cells by cytokines and bacterial lipopolysaccharide (LPS) and its expression triggers the coagulation. The cyclopentenone prostaglandins are naturally occurring prostaglandin D₂ (PGD₂) derivatives that comprises prostaglandin J₂ (PGJ₂) and its metabolites Δ¹²-PGJ₂ and 15-deoxyΔ^{12, 14}-prostaglandin J₂ (15d-PGJ₂). These compounds, detected in vivo in a later phase of the inflammatory response, are characterized by anti-inflammatory activity and participate to the resolution of inflammation. We have here investigated the effect of 15d-PGJ₂ on TF expression in human macrophages and endothelial cells (HUVEC). Our results indicate that 15d-PGJ₂ down-regulates LPSand TNFα-induced TF activity, protein and mRNA through inhibition of TF gene transcription. The effect of 15d-PGJ₂ is targeted to the NF-κB/I-κB pathway and to the mitogen activated protein kinase ERK1/2. A role of PPARγ activation in TF inhibition by 15d-PGJ₂ was excluded. We conclude that 15d-PGJ₂ negatively affects TF expression in macrophages and endothelial cells through a PPARγ-independent mechanism. This down-regulation may be crucial to limit excessive blood clotting activation in immuno-inflammatory diseases.

Keywords

Cyclopentenone prostaglandins - tissue factor - inflammation - thrombosis - macrophages - endothelial cells

Volltext

Referenzen

References
1 Edgington TS, Mackman N, Brand K, Ruf W. The structural biology of expression and function of tissue factor. Thromb Haemost 1991; 66: 67-79.
2 Carson SD, Brozna JP. The role of tissue factor in the production of thrombin. Blood Coagul Fibrinolysis 1993; 04: 281-92.
3 Drake TA, Cheng J, Chang A, Taylor jr FB. Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal E. coli sepsis. Am J Pathol 1993; 142: 1458-70.
4 Todoroki H, Nakamura S, Higure A, Okamoto K, Takeda S, Nagata N, Itoh H, Ohsato K. Neutrophils express tissue factor in a monkey model of sepsis. Surgery 2000; 127: 209-16.
5 Esmon CT. Introduction: are natural anticoagulants candidates for modulating the inflammatory response to endotoxin?. Blood 2000; 1477: 1113-6.
6 Creasey AA, Chang ACK, Feigen L, Wun TC, Taylor jr FB, Hinshaw LB. Tissue factor pathway inhibitor (TFPI) reduces mortality from E. coli septic shock. J Clin Invest 1993; 91: 2850-6.
7 Taylor FB, Chang AC, Peer G, Li A, Ezban M, Hedner U. Active site inhibited factor VIIa (DEGR VIIa) attenuates the coagulant and inteleukin6 and -8, but not tumor necrosis factor, responses of the baboon to LD₁₀₀ Escherichia coli. Blood 1998; 91: 1609-15.
8 Broze jr GJ. Tissue factor pathway of coagulation:factor VII, tissue factor, and tissue factor pathway inhibitor. In: Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD. (eds) Haemostasis and Thrombosis. vol 2 third edition Singapore: Churchill Livingstone; 1994: 349.
9 Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999; 340: 115-26.
10 Hansson GK. Immune mechanisms in atherosclerosis. Arterioscler Thromb Vasc Biol 2001; 12: 1876-90.
11 Plutzky J. Inflammatory pathways in atherosclerosis and acute coronary syndromes. Am J Cardiol 2001; 88: 10K-15K.
12 Shah PK. Plaque disruption and thrombosis: potential role of inflammation and infection. Cardiol Rev 2000; 01: 31-9.
13 Libby P, Simon DI. Inflammation and thrombosis: the clot thickens. Circulation 2001; 103: 1718-20.
14 Libby P. Atheroma: more than mush. Lancet 1996; 348: S4
15 Tremoli E, Camera M, Toschi V, Colli S. Tissue factor in atherosclerosis. Atherosclerosis 1999; 144: 273-83.
16 Gilroy DW, Colville-Nash PR, Willis D, Chivers J, Paul-Clark MJ, Willoughby D. Inducible cyclooxygenase may have anti-inflammatory properties. Nat Med 1999; 05: 698-701.
17 Ianaro A, Ialenti A, Maffia P, Pisano B, Di Rosa M. Role of cyclopentenone prostaglandins in rat carrageenin pleurisy. FEBS Lett 2001; 508: 61-6.
18 Fitzpatrick FA, Wynalda MA. Albumin-catalyzed metabolism of prostaglandin D₂ . J Biol Chem 1983; 258: 11713-8.
19 Jiang C, Ting AT, Seed B. PPAR-γ agonists inhibit production of monocyte inflammatory cytokines. Nature 1999; 391: 82-6.
20 Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature 1998; 391: 79-82.
21 Nagoshi H, Uehara Y, Kanai F, Maeda S, Ogura T, Goto A, Toyo-oka T, Esumi H, Shimizu T, Omata M. Prostaglandin D2 inhibits inducible nitric oxide synthase expression in rat vascular smooth muscle cells. Circ Res 1998; 82: 204-9.
22 Petrova TV, Akama KT, Van Eldik LJ. Cyclopentenone prostaglandins suppress activation of microglia: down-regulation of inducible nitric-oxide synthase by 15-deoxy-Δ^{12, 14}-prostaglandin J₂ . Proc Natl Acad Sci USA 1999; 96: 4668-73.
23 Straus DS, Pascual G, Li M, Welch JS, Ricote M, Hsiang C-H, Sengchanthalangsy LL, Ghosh G, Glass CK. 15-deoxy-Δ^{12, 14}-prostaglandin J₂ inhibits multiple steps in the NF-κB signaling pathway. Proc Natl Acad Sci USA 2000; 97: 4844-9.
24 Mackman N. Regulation of the tissue factor gene. FASEB J 1995; 09: 883-9.
25 Verma I, Stevenson J, Schwarz E, Van Antwerp D, Miyamoto S. Rel/NFΔB/IΔB family: intimate tales of association and dissociation. Genes Dev 1995; 09: 2723-35.
26 Colli S, Lalli M, Risè P, Mussoni L, Eligini S, Galli C, Tremoli E. Increased thrombogenic potential of human monocyte-derived macrophages spontaneously transformed into foam cells. Thromb Haemost 1999; 81: 576-81.
27 Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 1973; 52: 2745-56.
28 Tremoli E, Camera M, Maderna P, Sironi L, Prati L, Colli S, Piovella F, Bernini F, Corsini A, Mussoni L. Increased synthesis of plasminogen activator inhibitor-1 by cultured human endothelial cells exposed to native and modified LDLs. Arterioscler Thromb 1993; 13: 338-46.
29 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-54.
30 Dignam JD, Lebovitz RM, Roeder RG. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acid Res 1983; 11: 1475-88.
31 Pierce J, Suelter CH. An evaluation of the Coomassie Brilliant Blue G-250 dye-binding method for quantitative protein determination. Anal Biochem 1977; 81: 478-80.
32 Eligini S, Colli S, Basso F, Sironi L, Tremoli E. Oxidized low density lipoprotein suppresses expression of inducible cyclooxygenase in human macrophages. Arterioscler Thromb Vasc Biol 1999; 19: 1719-25.
33 Bartha K, Brisson C, Archipoff G, de la Salle C, Lanza F, Cazenave JP, Beretz A. Thrombin regulates tissue factor and thrombomodulin mRNA levels and activities in human saphenous vein endothelial cells by distinct mechanisms. J Biol Chem 1993; 268: 421-9.
34 Colli S, Eligini S, Lalli M, Camera M, Paoletti R, Tremoli E. Vastatins inhibit tissue factor in cultured human macrophages: A novel mechanism of protection against atherothrombosis. Arterioscler Thromb Vasc Biol 1997; 17: 265-72.
35 Sambrook T, Fritsch EF, Maniatis T. (Eds). Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor. 1989
36 Vu-Dac N, Chopin-Delannoy S, Gervois P, Bonnelye E, Martin G, Fruchart J-C, Laudet V, Staels B. The nuclear receptors peroxisome proliferatoractivated receptor a and apolipoprotein A-I expression by fibrates. J Biol Chem 1998; 273: 25713-20.
37 Castrillo A, Diaz-Guerra MJM, Hortelano S, Martin-Sanz P, Bosca L. Inhibition of IκB kinase and IκB phosphorylation by 15-Deoxy-Δ^{12, 14}-Prostaglandin J₂ in activated murine macrophages. Mol Cell Biol 2000; 20: 1692-98.
38 Rossi A, Kaphai P, Natoli G, Takahashi T, Chen Y, Karin M, Santoro MG. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase. Nature 2000; 403: 103-8.
39 Cernuda-Morollon E, Pineda-Molina E, Canada FJ, Perez-Sala D. 15deoxy-Δ^{12, 14}-prostaglandin J₂ inhibition of NF-κB-DNA binding through covalent modification of the p50 subunit. J Biol Chem 2001; 276: 35530-6.
40 Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM. 15-deoxy-Δ^{12, 14}-prostaglandin J₂ is a ligand for the adipocyte determination factor PPARγ. Cell 1995; 83: 803-12.
41 Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC, Lehmann JM. A prostaglandin J₂ metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation. Cell 1995; 83: 813-9.
42 Chawla A, Barak Y, Nagy L, Liao D, Tontonoz P, Evans RM. PPARγdependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat Med 2001; 07: 48-52.
43 Han J, Hajjar DP, Tauras JM, Feng J, Gotto jr AM, Nicholson AC. Tansforming growth factor-β1 (TGFβ1) and TGFβ2 decrease expression of CD36, the type B scavenger receptor, through mitogen-activated protein kinase phosphorylation of peroxisome proliferator-γ. J Biol Chem 1999; 275: 1241-6.
44 Crutchley DJ, Hirsch MJ. The stable prostacyclin analogue, Iloprost, and prostaglandin E1 inhibit monocyte procoagulant activity in vitro. Blood 1991; 78: 382-6.
45 Ricote M, Huang JT, Welch JS, Glass CK. The peroxisome proliferatoractivated receptor γ (PPARγ) as a regulator of monocyte/macrophage function. J Leukoc Biol 1999; 66: 733-9.
46 Oeth P, Parry GCN, Mackman N. Regulation of the 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.
47 Moll T, Czyz M, Holzmuller H, Hofer-Warbinek R, Wagner E, Winkler H, Bach FH, Hofer E. Regulation of the tissue factor promoter in endothelial cells. Binding of NF-κB-, AP-1-, and Sp1-like transcription factors. J Biol Chem 1995; 270: 3849-57.
48 Oeth P, Mackman N. Salicylates inhibit lipopolysaccharide-induced transcriptional activation of the tissue factor gene in human monocytic cells. Blood 1995; 86: 4144-52.
49 Mackman N. Protease inhibitors block lipopolysaccharide induction of tissue factor gene expression in human monocytic cells by preventing activation of c-Rel/p65 heterodimers. J Biol Chem 1994; 269: 26363-7.
50 Orthner CL, Rodgers GM, Fitzgerald LA. Pyrrolidine dithiocarbamate abrogates tissue factor (TF) expression by endothelial cells: evidence implicating nuclear factor-κB in TF induction by diverse agonists. Blood 1995; 86: 436-43.
51 Marx N, Mackman N, Schonbeck U, Yilmaz N, Hombach V, Libby P, Plutzky J. PPARα activators inhibit tissue factor expression and activity in human monocytes. Circulation 2001; 103: 213-9.
52 Xie S, O’Reagan DJ, Kakkar VV, Scully MF. 15-Deoxy-Δ^{12, 14} PGJ2 induces procoagulant activity in cultured human endothelial cells. Thromb Haemost 2002; 87: 523-9.
53 Levonen A-L, Dickinson DA, Moellering DR, Mulcahy RT, Forman HJ, Darley-Usmar VM. Biphasic effect of 15-deoxy-Δ^{12, 14}-prostaglandin J2 on glutathione induction and apoptosis in human endothelial cells. Arterioscler Thromb Vasc Biol 2001; 21: 1846-51.
54 Brisseau GF, Dackiw AP, Cheung PY, Christie N, Rotstein OD. Posttranscriptional regulation of macrophage tissue factor expression by antioxidants. Blood 1995; 85: 1025-35.
55 Mechtcheriakova D, Schabbauer G, Lucerna M, Clauss M, De Martin R, Binder BR, Hofer E. Specificity, diversity, and convergence in VEGF and TNF-α signaling events leading to tissue factor up-regulation via EGR-1 in endothelial cells. Faseb J 2001; 15: 230-42.
56 Guha M, O’Connell MA, Pawlinski R, Hollis A, McGovern P, Yan S-F, Stem D, Mackman N. 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.
57 Hortelano S, Castrillo A, Alvarez AM, Bosca L. Contribution of cyclopentenone prostaglandins to the resolution of inflammation through the potentiation of apoptosis in activated macrophages. J Immunol 2000; 165: 6525-31.
58 Kondo M, Oya-Ito T, Kumagai T, Osawa T, Uchida K. Cyclopentenone prostaglandins as potential inducers of intracellular oxidative stress. J Biol Chem 2001; 276: 12076-83.
59 Herschman HR, Reddy ST, Xie W. Function and regulation of prostaglandin synthase-2. Adv Exp Med Biol 1997; 407: 61-6.
60 Offenbacher S, Odle BM, Van Dyke TE. The use of crevicular fluid prostaglandin E2 levels as a predictor of periodontal attachment loss. J Periodontal Res 1986; 21: 101-12.
61 Fukushima M. Prostaglandin J2 anti-tumour and anti-viral activities and the mechanisms involved. Eicosanoids 1990; 03: 189-99.
62 Shibata T, Kondo M, Osawa T, Shibata N, Kobayashi M, Uchida K. 15-Deoxy-Δ^{12, 14}-prostaglandin J2: A prostaglandin D2 metabolite generated during inflammatory processes. J Biol Chem 2002; 271: 10459-66.
63 Ardissino D, Merlini PA, Bauer KA, Bramucci E, Ferrario M, Coppola R, Fetiveau R, Lucreziotti S, Rosenberg RD, Mannucci PM. Thrombogenic potential of human coronary atherosclerotic plaque. Blood 2001; 98: 2726-29.
64 Moreno PR, Palacios IF, Leon MN, Rhodes J, Fuster V, Fallon JT. Histopathologic comparison of human coronary in-stent and post-ballon angioplasty restenotic tissue. Am J Cardiol 1999; 84: 462-6.
65 Mizuno O, Ikeda U, Hojo Y, Fujikawa H, Katsuki T, Shimada K. Tissue factor expression in coronary circulation as a prognostic factor for late restenosis after coronary angioplasty. Cardiology 2001; 95: 84-9.
66 Banai S, Gertz SD. Tissue factor as a therapeutic target in coronary syndromes. Am J Cardiol 2001; 87: 763-5.
67 Cipollone F, Marini M, Iezzi A, Fazia M, Pini B, De Cesare D, Paloscia L, Materazzo G, D’Annunzio E, Cuccurullo F, Mezzetti A. Preprocedural low plasma level of 15-deoxy-Δ^{12, 14}-prostaglandin J2 is associated with enhanced inflammatory response and restenosis after PTCA. Abs PPARs: from Basic Science to Clinical Applications, Florence, Italy, April. 2001