Activity of matrix metalloproteinase-9 is elevated in sera of patients with systemic lupus erythematosus

Clinical and Experimental Immunology - Tập 127 Số 2 - Trang 393-398 - 2002
Anat Faber-Elmann1, Zev Sthoeger1,2, A TCHERNIACK1,2, Molly Dayan1, Edna Mozes1
1Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
2Department of Medicine B, Kaplan Medical Centre, Rehovot, Israel

Tóm tắt

SummarySystemic lupus erythematosus (SLE) is an autoimmune disease characterized by the increased production of autoantibodies and by systemic clinical manifestations and damage to multiple organs. The aim of the present study was to analyse matrix metalloproteinase (MMP)-9 activity in sera of patients with active and inactive SLE in order to evaluate its role in the pathogenesis and course of the disease, as well as its diagnostic value. We measured activity levels of MMP-9 and MMP-2, using both gel zymography and activity assay kits, in sera of 40 SLE patients and of 25 healthy controls. We found that MMP-9 activity, but not MMP-2 activity, is significantly elevated in the sera of SLE patients compared with sera samples of healthy controls. High activity levels of MMP-9 were determined in sera of 68% of the SLE patients. Elevated levels of MMP-9 were correlated with the presence of discoid rash, Raynaud phenomenon, pneumonitis, mucosal ulcers and anti-phospholipid antibodies. Changes in activity levels of MMP-9, but not of MMP-2, were observed in sera of the same patient at different periods of the disease course. High levels of MMP-9 did not correlate with disease activity index (SLEDAI, BILAG) in female patients, but correlated with SLE activity in the group of male patients. The results of the present study suggest that MMP-9 plays a role in the pathogenesis of SLE.

Từ khóa


Tài liệu tham khảo

Hahn, 1993, An overview of the pathogenesis of systemic lupus erythematosus, Dubois’ lupus erythematosus, 69

Winchester, 1996, Systemic lupus erythematosus pathogenesis, 1361

Dean, 2000, Cytokines and systemic lupus erythematosus, Ann Rheum Dis, 59, 243, 10.1136/ard.59.4.243

Segal, 1997, Kinetics of cytokine production in experimental systemic lupus erythematosus: involvement of T helper cell 1/T helper cell 2-type cytokines in disease., J Immunol, 158, 3009, 10.4049/jimmunol.158.6.3009

Theofilopoulos, 1999, Tumor necrosis factor and other cytokines in murine lupus, Ann Rheum Dis, 58, 149

Eilat, 2001, The mechanism by which a peptide based on the complementarity determining region-1 of a pathogenic anti-DNA autoantibody ameliorates experimental SLE, Proc Natl Acad Sci, 98, 1148, 10.1073/pnas.98.3.1148

MacNaul, 1990, Discoordinate expression of stromelysin, collagenase, and tissue inhibitor of metalloproteinase-1 in rheumatoid synovial fibroblasts. Synergistic effects of interleukin-1 and tumor necrosis factor-alpha on stromelysin expression., J Biol Chem, 265, 17238, 10.1016/S0021-9258(17)44894-0

Zhang, 1998, Differential regulation of monocyte matrix metalloproteinase and TIMP-1 production by TNF-α, granulocyte-macrophage CSF, and IL-1β through prostaglandin-dependent and -independent mechanisms., J Immunol, 161, 3071, 10.4049/jimmunol.161.6.3071

Shingleton, 1996, Collagenases: a key enzyme in collagen turnover., Biochem Cell Biol, 74, 759, 10.1139/o96-083

Goetzl, 1996, Matrix metalloproteinases in immunity., J Immunol, 156, 1, 10.4049/jimmunol.156.1.1

Massova, 1998, Matrix metalloproteinases: structures, evolution, and diversification., FASEB J, 12, 1075, 10.1096/fasebj.12.12.1075

Guedez, 1996, The role of metalloproteinases and their inhibitors in hematological disorders., Crit Rev Oncogenesis, 7, 205, 10.1615/CritRevOncog.v7.i3-4.40

Ozenci, 1999, Metalloproteinases and their tissue inhibitors in multiple sclerosis., J Autoimmun, 12, 297, 10.1006/jaut.1999.0285

Gijbels, 1994, Reversal of experimental autoimmune encephalomyelitis with a hydroxamate inhibitor of matrix metalloproteinases., J Clin Invest, 94, 2177, 10.1172/JCI117578

Keyszer, 1999, Circulating levels of matrix metalloproteinases MMP-3 and MMP-1, tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP-1/TIMP-1 complex in rheumatic disease. Correlation with clinical activity of rheumatoid arthritis versus other surrogate markers., J Rheumatol, 26, 251

Liu, 1998, Gelatinase B-deficient mice are resistant to experimental bullous Pemphigoid., J Exp Med, 188, 475, 10.1084/jem.188.3.475

Creange, 1999, Matrix metalloproteinase-9 is increased and correlates with severity in Guillain-Barre syndrome., Neurology, 53, 1683, 10.1212/WNL.53.8.1683

Hughes, 1998, Matrix metalloproteinase expression during experimental neuritis., Brain, 121, 481, 10.1093/brain/121.3.481

Ichikawa, 1998, Serum matrix metalloproteinase-3 and fibrin degradation product levels correlate with clinical disease activity in rheumatoid arthritis., Clin Exp Rheumatol, 16, 533

Zucker, 1999, Increased serum stromelysin-1 levels in systemic lupus erythematosus: lack of correlation with disease activity., J Rheumatol, 26, 78

Zucker, 1999, Measurement of matrix metalloproteinases and tissue inhibitors of metalloproteinases in blood and tissues. Clinical and experimental applications., Ann N Y Acad Sci, 878, 212, 10.1111/j.1749-6632.1999.tb07687.x

Wallace, 1999, The matrix metalloproteinase inhibitor BB-1101 prevents experimental autoimmune uveoretinitis (EAU)., Clin Exp Immunol, 118, 364, 10.1046/j.1365-2249.1999.01066.x

Conway, 1995, Inhibition of cartilage and bone destruction in adjuvant arthritis in the rat by a matrix metalloproteinase inhibitor., J Exp Med, 182, 449, 10.1084/jem.182.2.449

Bombardier, 1992, Derivation of the SLEDAI. A disease activity index for lupus patients., Arthritis Rheum, 35, 630, 10.1002/art.1780350606

Hay, 1993, The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus., Q J Med, 86, 447

Ebihara, 1998, Increased plasma metalloproteinase-9 concentrations precede development of microalbuminuria in non-insulin-dependent diabetes mellitus., Am J Kidney Dis, 32, 544, 10.1016/S0272-6386(98)70015-0

Ebihara, 1999, Effect of oral adsorbent AST-120 on plasma metalloproteinase-9 and serum tissue inhibitor of metalloproteinase-1 concentrations in chronic renal failure, Nephron, 83, 169, 10.1159/000045497

Gijbels, 1992, Gelatinase in the cerebrospinal fluid of patients with multiple sclerosis and other inflammatory neurological disorders., J Neuroimmunol, 41, 29, 10.1016/0165-5728(92)90192-N

Paemen, 1994, Evaluation of gelatinases and IL-6 in the cerebrospinal fluid of patients with optic neuritis, multiple sclerosis and other inflammatory neurological disease., Eur J Neurol, 1, 55, 10.1111/j.1468-1331.1994.tb00051.x

Akiyama, 1997, Changes in serum concentrations of matrix metalloproteinases, tissue inhibitors of metalloproteinases and type IV collagen in patients with various types of glomerulonephritis., Res Commun Mol Pathol Pharmacol, 95, 115

Fleischmajer, 2000, Basement membrane alterations in psoriasis are accompanied by epidermal overexpression of MMP-2 and its inhibitor TIMP-2, J Invest Dermatol, 115, 771, 10.1046/j.1523-1747.2000.00138.x

Kotajima, 1998, Increased levels of matrix metalloproteinase-3 in sera from patients with active lupus nephritis., Clin Exp Rheum, 16, 409

Nakamura, 1993, Gene expression of metalloproteinases and their inhibitor in renal tissue of New Zealand Black/White F1 mice., Clin Sci, 85, 295, 10.1042/cs0850295

McMillan, 1996, Characterization of a glomerular epithelial cell metalloproteinase as matrix metalloproteinase-9 with enhanced expression in a model of membranous nephropathy., J Clin Invest, 97, 1094, 10.1172/JCI118502

Lovett, 1992, Structural characterization of the mesangial cell type IV collagenase and enhanced expression in a model of immune complex mediated glomerulonephritis., Am J Pathol, 141, 85

Hurewitz, 1992, Human pleural effusions are rich in matrix metalloproteinases., Chest, 102, 1808, 10.1378/chest.102.6.1808

Imada, 1997, Hormonal regulation of matrix metalloproteinase 9/gelatinase B gene expression in rabbit uterine cervical fibroblasts., Biol Reprod, 56, 575, 10.1095/biolreprod56.3.575

Marbaix, 1992, Progesterone regulates the activity of collagenase and related gelatinases A and B in human endometrial explants., Proc Natl Acad Sci USA, 89, 11789, 10.1073/pnas.89.24.11789

Saren, 1996, TNF-α and IL-1β selectively induce expression of 92-kDa gelatinase by human macrophages., J Immunol, 157, 4159, 10.4049/jimmunol.157.9.4159

Marti, 1992, Molecular characterization of a low-molecular-mass matrix metalloproteinase secreted by glomerular mesangial cells as PUMP-1., Biochem J, 285, 899, 10.1042/bj2850899

Gearing, 1994, Processing of tumour necrosis factor alpha precursor by metalloproteinases., Nature, 370, 555, 10.1038/370555a0

Thông tin
Thông tin xuất bản

Clinical and Experimental Immunology

Tập 127 Số 2

393-398

Thông tin tác giả