A peptide based on an anti-DNA autoantibody downregulates matrix metalloproteinases in murine models of lupus.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the increased production of autoantibodies and by T cell dysfunction associated with general clinical manifestations. A model of induced experimental SLE by the immunization with the human monoclonal anti-DNA 16/6Id(+) autoantibody and a model of the SLE-prone mice (NZB x NZW)F1 were used in the present study. Two peptides based on the complementarity determining regions (CDR) 1 and 3 of a murine monoclonal anti-DNA 16/6Id(+) autoantibody were shown to ameliorate spontaneous and induced SLE in mice. We demonstrate here that levels of matrix metalloproteinase (MMP)-3 and MMP-9 were elevated in plasma and kidneys of SLE-afflicted mice. Levels of both MMP-3 and MMP-9 were elevated in kidneys of mice with the 16/6Id induced experimental SLE already in the early phases of disease development. However, increased levels of only MMP-3 were detected in the plasma at the early stages of disease, while MMP-9 activity was elevated later, when clinical manifestations were already observed. Treatment of SLE-afflicted mice, with the CDR1-based peptide that ameliorates disease manifestations in mice, led to a reduction in MMP-9 activity and in MMP-3 protein levels both in plasma and in kidneys. We thus suggest that these enzymes may play a pathogenic role in the disease and may serve as markers for the determination of disease progression or amelioration.
Faber-Elmann
Anat
A
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Eilat
Eran
E
Zinger
Heidy
H
Mozes
Edna
E
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D005260:Female; D005656:Fungal Proteins; D007114:Immunization; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
D000974:Antibodies, Antinuclear; D015415:Biomarkers; C094693:CDR1 protein, Candida albicans; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D010455:Peptides; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9