To elucidate the pathomechanisms of secondary progressive (SP) multiple sclerosis (MS), we have investigated the expression of chemokines, chemokine receptors, matrix metalloproteinase-9 (MMP-9) and immunoglobulins in the demyelinating plaques.
We studied the relationships between serum MMP-9, MMP-2, TIMP-1 and TIMP-2 and different magnetic resonance imaging (MRI) measures of disease activity in MS patients during treatment with rIFNbeta-1a.
Dopamine reduced T cell proliferation, secretion of interferon-gamma (IFN-gamma), and production of matrix metalloproteinase-9 (MMP-9) mRNA in PBMCs from controls but not from MS patients.
Changes of matrix metalloproteinase-9 and its tissue inhibitor (TIMP-1) after autologous hematopoietic stem cell transplantation in multiple sclerosis.
One of the molecular mechanisms by which IFN-beta exerts its beneficial effect in multiple sclerosis is reduction of MMP-9 expression and increase of its endogenous tissue inhibitor, TIMP-1.
We review how chemokines and MMP-9 may be involved in the pathogenesis of MS by controlling leukocyte migration between different functional compartments.
Matrix metalloproteinase gelatinase B (MMP-9) is upregulated in MS and was recently shown to degrade interferon beta, one of the drugs used to treat MS. Consequently, the effect of endogenously produced interferon beta or parenterally given interferon beta may be increased by gelatinase B inhibitors.
No allelic associations were found between MS and the CA microsatellite marker in the promoter region of the gelatinase B gene, and the polymorphic CA repeat in the sixth intron of PECAM1.
Similarly, MS is associated with high percentages of MMP-2 and -3 and of TIMP-1 expressing mDC by flow cytometry together with high MMP-3 secretion and high MMP-9 activity in culture supernatants.
In a case-control analysis of 345 Swedish individuals and in a study of 125 Sardinian simplex families no genetic associations between the gelatinase B gene polymorphisms and MS susceptibility were found.
The highest levels of MMP-9 were found in the CSF of patients with cryptococcosis, cytomegalovirus encephalitis and tuberculous meningitis and were comparable with those found in the CSF of HIV-negative patients with multiple sclerosis or meningitis.
These observations on the coexpression of enzymes and inhibitors of the matrix degrading cascade in CNS tissue pinpoint t-PA, a rate-limiting enzyme, and gelatinase B as therapeutic targets in MS.