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Matrix Metalloproteinase-9 and Autoimmune Diseases

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Matrix metalloproteinases (also named matrixin or MMPs) are a major group of enzymes that regulate cell-matrix composition by using zinc for their proteolytic activities. They are essential for various normal biological processes such as embryonic development, morphogenesis, reproduction tissue resorption, and remodeling. Metalloproteinases also play a role in pathological processes including inflammation, arthritis, cardiovascular diseases, pulmonary diseases and cancer. Herein we review the involvement of MMP-9 in a variety of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, systemic sclerosis, rheumatoid arthritis, multiple sclerosis, polymyositis and atherosclerosis. MMP-9 plays either a primary or secondary role in each one of those autoimmune diseases by its up or down-regulation. It is not expressed constantly but rather is induced or suppressed by many regulating molecules. This feature of MMP-9 along with its involvement in disease pathogenesis turns it into a target for therapy of autoimmune diseases.

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REFERENCES

  1. Chakraborti S, Mandal M, Das S, Mandal A, Chakraborti T: Regulation of matrix metalloproteinases: An overview. Mol Cell Biochem 253:269–285, 2003.

    Article  PubMed  CAS  Google Scholar 

  2. Mott JD, Werb Z: Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 16:558–564, 2004.

    Article  PubMed  CAS  Google Scholar 

  3. Nagase H, Woessner JF, Jr: Matrix metalloproteinases. J Biol Chem 274:21491–21494, 1999.

    Article  PubMed  CAS  Google Scholar 

  4. Mandal M, Mandal A, Das S, Chakraborti T, Sajal C: Clinical implications of matrix metalloproteinases. Mol Cell Biochem 252:305–329, 2003.

    Article  PubMed  CAS  Google Scholar 

  5. Van den Steen PE, Dubois B, Nelissen I, Rudd PM, Dwek RA, Opdenakker G: Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit Rev Biochem Mol Biol 37:375–536, 2002.

    Article  PubMed  CAS  Google Scholar 

  6. Opdenakker G, Van den Steen PE, Van Damme J: Gelatinase B: A tuner and amplifier of immune functions. Trends Immunol 22:571–579, 2001.

    Article  PubMed  CAS  Google Scholar 

  7. Opdenakker G, Van den Steen PE, Dubois B, Nelissen I, Van Coillie E, Masure S, Proost P, Van Damme J: Gelatinase B functions as regulator and effector in leukocyte biology. J Leukoc Biol 69:851–859, 2001.

    PubMed  CAS  Google Scholar 

  8. Nguyen M, Arkell J, Jackson CJ: Human endothelial gelatinases and angiogenesis. Int J Biochem Cell Biol 33:960–970, 2001.

    Article  PubMed  CAS  Google Scholar 

  9. Matache C, Stefanescu M, Dragomir C, Tanaseanu S, Onu A, Ofiteru A, Szegli G: Matrix metalloproteinase-9 and its natural inhibitor TIMP-1 expressed or secreted by peripheral blood mononuclear cells from patients with systemic lupus erythematosus. J Autoimmun 20:323–331, 2003.

    Article  PubMed  CAS  Google Scholar 

  10. Faber-Elmann A, Sthoeger Z, Tcherniack A, Dayan M, Mozes E: Activity of matrix metalloproteinase-9 is elevated in sera of patients with systemic lupus erythematosus. Clin Exp Immunol 127:393–398, 2002.

    Article  PubMed  CAS  Google Scholar 

  11. Makowski GS, Ramsby ML: Concentrations of circulating matrix metalloproteinase 9 inversely correlate with autoimmune antibodies to double stranded DNA: Implications for monitoring disease activity in systemic lupus erythematosus. Mol Pathol 56:244–247, 2003.

    Article  PubMed  CAS  Google Scholar 

  12. Konttinen YT, Halinen S, Hanemaaijer R, Sorsa T, Hietanen J, Ceponis A, Xu JW, Manthorpe R, Whittington J, Larsson A, Salo T, Kjeldsen L, Stenman UH, Eisen AZ: Matrix metalloproteinase (MMP)-9 type IV collagenase/gelatinase implicated in the pathogenesis of Sjogren's syndrome. Matrix Biol 17:335–347, 1998.

    Article  PubMed  CAS  Google Scholar 

  13. Perez P, Goicovich E, Alliende C, Aguilera S, Leyton C, Molina C, Pinto R, Romo R, Martinez B, Gonzalez MJ: Differential expression of matrix metalloproteinases in labial salivary glands of patients with primary Sjogren's syndrome. Arthritis Rheum 43:2807–2817, 2000.

    Article  PubMed  CAS  Google Scholar 

  14. Hanemaaijer R, Visser H, Konttinen YT, Koolwijk P, Verheijen JH: A novel and simple immunocapture assay for determination of gelatinase-B (MMP-9) activities in biological fluids: Saliva from patients with Sjogren's syndrome contain increased latent and active gelatinase-B levels. Matrix Biol 17:657–665, 1998.

    Article  PubMed  CAS  Google Scholar 

  15. Kikuchi K, Kubo M, Hoashi T, Tamaki K: Decreased MMP-9 activity in the serum of patients with diffuse cutaneous systemic sclerosis. Clin Exp Dermatol 27:301–305, 2002.

    Article  PubMed  CAS  Google Scholar 

  16. Kim WU, Min SY, Cho ML, Hong KH, Shin YJ, Park SH, Cho CS: Elevated matrix metalloproteinase-9 in patients with systemic sclerosis. Arthritis Res Ther 7:R71–R79, 2005. Epub 2004 Nov 10.

    Article  PubMed  CAS  Google Scholar 

  17. Kieseier BC, Schneider C, Clements JM, Gearing AJ, Gold R, Toyka KV, Hartung HP: Expression of specific matrix metalloproteinases in inflammatory myopathies. Brain 124:341–351, 2001.

    Article  PubMed  CAS  Google Scholar 

  18. Choi YC, Dalakas MC: Expression of matrix metalloproteinases in the muscle of patients with inflammatory myopathies. Neurology 54:65–71, 2000.

    PubMed  CAS  Google Scholar 

  19. Tchetverikov I, Lard LR, DeGroot J, Verzijl N, TeKoppele JM, Breedveld FC, Huizinga TW, Hanemaaijer R: Matrix metalloproteinases-3, -8, -9 as markers of disease activity and joint damage progression in early rheumatoid arthritis. Ann Rheum Dis 62:1094–1099, 2003.

    Article  PubMed  CAS  Google Scholar 

  20. Gruber BL, Sorbi D, French DL, Marchese MJ, Nuovo GJ, Kew RR, Arbeit LA: Markedly elevated serum MMP-9 (gelatinase B) levels in rheumatoid arthritis: A potentially useful laboratory marker. Clin Immunol Immunopathol 78:161–171, 1996.

    Article  PubMed  CAS  Google Scholar 

  21. Leppert D, Ford J, Stabler G, Grygar C, Lienert C, Huber S, Miller KM, Hauser SL, Kappos L: Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis. Brain 121(Pt 12):2327–2334, 1998.

    Article  PubMed  Google Scholar 

  22. Sastre-Garriga J, Comabella M, Brieva L, Rovira A, Tintore M, Montalban X: Decreased MMP-9 production in primary progressive multiple sclerosis patients. Mult Scler 10:376–380, 2004.

    Article  PubMed  CAS  Google Scholar 

  23. Liuzzi GM, Trojano M, Fanelli M, Avolio C, Fasano A, Livrea P, Riccio P: Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple sclerosis: Implication for pathogenesis. Mult Scler 8:222–228, 2002.

    Article  PubMed  CAS  Google Scholar 

  24. Kieseier BC, Kiefer R, Clements JM, Miller K, Wells GM, Schweitzer T, Gearing AJ, Hartung HP: Matrix metalloproteinase-9 and -7 are regulated in experimental autoimmune encephalomyelitis. Brain 121(Pt 1):159–166, 1998.

    Article  PubMed  Google Scholar 

  25. Sherer Y, Shoenfeld Y: Immunomodulation for treatment and prevention of atherosclerosis. Autoimmun Rev 1:21–27, 2002.

    Article  PubMed  CAS  Google Scholar 

  26. Jiang X, Zeng HS, Guo Y, Zhou ZB, Tang BS, Li FK: The expression of matrix metalloproteinases-9, transforming growth factor-beta1 and transforming growth factor-beta receptor I in human atherosclerotic plaque and their relationship with plaque stability. Chin Med J (Engl) 117:1825–1829, 2004.

    CAS  Google Scholar 

  27. Chen F, Eriksson P, Hansson GK, Herzfeld I, Klein M, Hansson LO, Valen G: Expression of matrix metalloproteinase 9 and its regulators in the unstable coronary atherosclerotic plaque. Int J Mol Med 15:57–65, 2005.

    PubMed  CAS  Google Scholar 

  28. Sebastian Stintzing, MD, peter Heuschmann, MD, Letterio Barbera, MD, Matthias Ocker, MD Andreas Jung, PhD, Thomas Kirchner, MD, and Daniel Neureiter, MD, Erlangen, Muenster, and Bochum, Germany: Overexpression of MMP9 and Tissue Factor in unstable carotid plaques associated with Chlamydia pneumoniae, inflammation, and apoptosis. Ann Vasc Surg 19:1–10, 2005.

    Article  Google Scholar 

  29. Shapiro S, Shoenfeld Y, Gilburd B, Sobel E, Lahat N: Intravenous gamma globulin inhibits the production of matrix metalloproteinase-9 in macrophages. Cancer 95:2032–2037, 2002.

    Article  PubMed  CAS  Google Scholar 

  30. Aljada A, Ghanim H, Mohanty P, Hofmeyer D, Tripathy D, Dandona P: Hydrocortisone suppresses intranuclear activator-protein-1 (AP-1) binding activity in mononuclear cells and plasma matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9). J Clin Endocrinol Metab 86:5988–5991, 2001.

    Article  PubMed  CAS  Google Scholar 

  31. Profita M, Gagliardo R, Di Giorgi R, Bruno A, Riccobono L, Bonanno A, Bousquet J, Vignola AM: In vitro effects of flunisolide on MMP-9, TIMP-1, fibronectin, TGF-beta1 release and apoptosis in sputum cells freshly isolated from mild to moderate asthmatics. Allergy 59:927–932, 2004.

    Article  PubMed  CAS  Google Scholar 

  32. Rosenberg GA, Dencoff JE, Correa N, Reiners M, Ford CC: Effect of steroid on CNS matrix metalloproteinases in multiple sclerosis: Relation to blood-brain barrier injury. Neurology 46:1626–1632, 1996.

    PubMed  CAS  Google Scholar 

  33. Kieseier BC, Archelos JJ, Hartung HP: Different effects of simvastatin and interferon beta on the proteolytic activity of matrix metalloproteinases. Arch Neurol 61:929–932, 2004.

    Article  PubMed  Google Scholar 

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ACKNOWLEDGMENT

This study was supported in part by the Ernesto Hecht Research Grant (to Y Sherer).

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Authors and Affiliations

  1. Department of Medicine ‘B’ & Center for Autoimmune Diseases, Sheba Medical Center Tel-Hashomer, Sackler Faculty of Medicine, Tel-Aviv University, Jerusalem, Israel

    Maya Ram, Yaniv Sherer & Yehuda Shoenfeld

  2. Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Tel-Aviv, Israel

    Yehuda Shoenfeld

  3. Department of Medicine ‘B’ & Center for Autoimmune Diseases, Sheba Medical Center, 52621, Tel-Hashomer, Israel

    Yehuda Shoenfeld

Authors
  1. Maya Ram
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  2. Yaniv Sherer
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  3. Yehuda Shoenfeld
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Correspondence to Yehuda Shoenfeld.

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Ram, M., Sherer, Y. & Shoenfeld, Y. Matrix Metalloproteinase-9 and Autoimmune Diseases. J Clin Immunol 26, 299–307 (2006). https://doi.org/10.1007/s10875-006-9022-6

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  • DOI: https://doi.org/10.1007/s10875-006-9022-6

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