J Neurol Neurosurg Psychiatry. 2000 Mar;68(3):368-71.
Upregulation of matrix metalloproteinase-9 in the cerebrospinal fluid of patients with acute Lyme neuroborreliosis.Kirchner A1, Koedel U, Fingerle V, Paul R, Wilske B, Pfister HW
Abstract
It was investigated
(1) whether metalloproteinase-9 (MMP-9), MMP-3, and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1, the natural tissue inhibitor of MMP-9) are increased in the CSF of patients with Lyme neuroborreliosis and
(2) whether macrophages can express MMP-9 when stimulated with Borrelia burgdorferi. Zymography showed MMP-9 activity in 26 of 31 (84%) CSF samples from patients with acute stage 2 Lyme neuroborreliosis, but not in 20 controls with non-inflammatory neurological disorders.
Activity of MMP-2 was detected in all CSF samples in both patients with neuroborreliosis and controls, suggesting a constitutive release of MMP-2.
Using enzyme linked immunosorbent assay (ELISA) MMP-3 (which can activate MMP-9) was detected in low concentrations in the CSF of 13 of 29 patients with neuroborreliosis, but not in controls.
TIMP-1 was increased twofold in CSF samples from patients with neuroborreliosis in comparison with the controls.
MMP-9 activity was induced in vitro in a mouse macrophage cell line (RAW 264.7) when stimulated with two different genospecies of B burgdorferi (B garinii, B afzelii ). This MMP-9 activity was reduced in a dose dependent manner when macrophages stimulated with B burgdorferi were coincubated with NF-kappaB SN50, a cell permeable peptide which inhibits the translocation of NF-kappaB into the nucleus of stimulated cells.
The data show that (1) MMP-9 activity is present in the CSF of patients with neuroborreliosis,
(2) macrophages stimulated with B burgdorferi are a possible source of MMP-9 increase, and
(3) activation of NF-kappaB may play a part in the upregulation of MMP-9 by B burgdorferi.
(1) whether metalloproteinase-9 (MMP-9), MMP-3, and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1, the natural tissue inhibitor of MMP-9) are increased in the CSF of patients with Lyme neuroborreliosis and
(2) whether macrophages can express MMP-9 when stimulated with Borrelia burgdorferi. Zymography showed MMP-9 activity in 26 of 31 (84%) CSF samples from patients with acute stage 2 Lyme neuroborreliosis, but not in 20 controls with non-inflammatory neurological disorders.
Activity of MMP-2 was detected in all CSF samples in both patients with neuroborreliosis and controls, suggesting a constitutive release of MMP-2.
Using enzyme linked immunosorbent assay (ELISA) MMP-3 (which can activate MMP-9) was detected in low concentrations in the CSF of 13 of 29 patients with neuroborreliosis, but not in controls.
TIMP-1 was increased twofold in CSF samples from patients with neuroborreliosis in comparison with the controls.
MMP-9 activity was induced in vitro in a mouse macrophage cell line (RAW 264.7) when stimulated with two different genospecies of B burgdorferi (B garinii, B afzelii ). This MMP-9 activity was reduced in a dose dependent manner when macrophages stimulated with B burgdorferi were coincubated with NF-kappaB SN50, a cell permeable peptide which inhibits the translocation of NF-kappaB into the nucleus of stimulated cells.
The data show that (1) MMP-9 activity is present in the CSF of patients with neuroborreliosis,
(2) macrophages stimulated with B burgdorferi are a possible source of MMP-9 increase, and
(3) activation of NF-kappaB may play a part in the upregulation of MMP-9 by B burgdorferi.
- PMID:
- 10675223
- PMCID:
- PMC1736835
- [Indexed for MEDLINE]
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