Gelatinase B/matrix metalloproteinase-9 cleaves interferon-β and is a target for immunotherapy

被引:88
作者
Nelissen, I
Martens, E
Van Den Steen, PE
Proost, P
Ronsse, I
Opdenakker, G
机构
[1] Katholieke Univ Leuven, Rega Inst Med Res, Labs Mol Immunol, B-3000 Louvain, Belgium
[2] Katholieke Univ Leuven, Rega Inst Med Res, Immunobiol Lab, B-3000 Louvain, Belgium
关键词
gelatinase B; interferon; multiple sclerosis; inflammation; viral infection;
D O I
10.1093/brain/awg129
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Parenteral administration of interferon (IFN)-beta is one of the currently approved therapies for multiple sclerosis. One characteristic of this disease is the increased production of gelatinase B, also called matrix metalloproteinase (MMP) 9. Gelatinase B is capable of destroying the blood-brain barrier, and of cleaving myelin basic protein into immunodominant and encephalitogenic fragments, thus playing a functional role and being a therapeutic target in multiple sclerosis. Here we demonstrate that gelatinase B proteolytically cleaves IFN-beta, kills its activity, and hence counteracts this cytokine as an antiviral and immunotherapeutic agent. This proteolysis is more pronounced with IFN-beta-1b than with IFN-beta-1a. Furthermore, the tetracycline minocycline, which has a known blocking effect in experimental autoimmune encephalomyelitis, an in vivo model of acute inflammation in multiple sclerosis, and other MMP inhibitors prevent the in vitro degradation of IFN-beta by gelatinase B. These data provide a novel mechanism and rationale for the inhibition of gelatinase B in diseases in which IFN-beta has a beneficial effect. The combination of gelatinase B inhibitors with better and lower pharmacological formulations of IFN-beta may reduce the side-effects of treatment with IFN-beta, and is therefore proposed for multiple sclerosis therapy and the immunotherapy of viral infections.
引用
收藏
页码:1371 / 1381
页数:11
相关论文
共 47 条
  • [1] Armstrong J A, 1981, Methods Enzymol, V78, P381
  • [2] THE INTERFERONS - MECHANISMS OF ACTION AND CLINICAL-APPLICATIONS
    BARON, S
    TYRING, SK
    FLEISCHMANN, WR
    COPPENHAVER, DH
    NIESEL, DW
    KLIMPEL, GR
    STANTON, GJ
    HUGHES, TK
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1991, 266 (10): : 1375 - 1383
  • [3] Human monocyte-derived dendritic cells produce bioactive gelatinase B:: Inhibition by IFN-ß
    Bartholomé, EJ
    Van Aelst, I
    Koyen, E
    Kiss, R
    Willems, F
    Goldman, M
    Opdenakker, G
    [J]. JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2001, 21 (07) : 495 - 501
  • [4] Production of matrix metalloproteinase-9 in early stage B-CLL: suppression by interferons
    Bauvois, B
    Dumont, J
    Mathiot, C
    Kolb, JP
    [J]. LEUKEMIA, 2002, 16 (05) : 791 - 798
  • [5] HUMAN INTERFERON - MASS-PRODUCTION IN A NEWLY ESTABLISHED CELL LINE, MG-63
    BILLIAU, A
    EDY, VG
    HEREMANS, H
    VANDAMME, J
    DESMYTER, J
    GEORGIADES, JA
    DESOMER, P
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1977, 12 (01) : 11 - 15
  • [6] Targeting leukocyte MMPs and transmigration - Minocycline as a potential therapy for multiple sclerosis
    Brundula, V
    Rewcastle, NB
    Metz, LM
    Bernard, CC
    Yong, VW
    [J]. BRAIN, 2002, 125 : 1297 - 1308
  • [7] Matrix metalloproteinase expression during experimental autoimmune encephalomyelitis and effects of a combined matrix metalloproteinase and tumour necrosis factor-alpha inhibitor
    Clements, JM
    Cossins, JA
    Wells, GMA
    Corkill, DJ
    Helfrich, K
    Wood, LM
    Pigott, R
    Stabler, G
    Ward, GA
    Gearing, AJH
    Miller, KM
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 1997, 74 (1-2) : 85 - 94
  • [8] Plasminogen activators and matrix metalloproteases, mediators of extracellular proteolysis in inflammatory demyelination of the central nervous system
    Cuzner, ML
    Opdenakker, G
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 1999, 94 (1-2) : 1 - 14
  • [9] In vivo neutrophil recruitment by granulocyte chemotactic protein-2 is assisted by gelatinase B/MMP-9 in the mouse
    D'Haese, A
    Wuyts, A
    Dillen, C
    Dubois, B
    Billiau, A
    Heremans, H
    Van Damme, J
    Arnold, B
    Opdenakker, G
    [J]. JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2000, 20 (07) : 667 - 674
  • [10] CD26, let it cut or cut it down
    De Meester, I
    Korom, S
    Van Damme, J
    Scharpé, S
    [J]. IMMUNOLOGY TODAY, 1999, 20 (08): : 367 - 375