Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis

Abstract

Matrix metalloproteinases (MMPs) are a family of endopeptidases capable of enzymatic digestion of subendothelial basement membrane and other components of the extracellular matrix. Expression of MMP-2, -3, -7 and -9 is increased around multiple sclerosis plaques and in brain tissue in experimental allergic encephalomyelitis. To measure quantitatively the expression of these MMPs and their endogenous inhibitors (TIMP-1 and -2), we analysed samples from 52 patients with relapsing-remitting and primary progressive multiple sclerosis by ELISA (enzyme-linked immunosorbent assay) and substrate-gel electrophoresis (zymography). MMP-9 was increased over controls in 100% of relapsing-remitting multiple sclerosis cases, with similar levels detected in relapses and clinically stable phases of disease. In primary progressive multiple sclerosis, MMP-9 was increased in 57% of CSF samples, but concentrations were below those encountered in the relapsing-remitting form. The selective upregulation of MMP-9 suggests that T-cells and macrophages invading the brain parenchyma and the CSF space are the predominant source of MMP-9 in multiple sclerosis. TIMPs and other MMPs (MMP-2 and -3) were not upregulated or not detectable (MMP-7) in CSF of patients with relapsing-remitting and primary progressive multiple sclerosis. The sustained increase of MMP-9 in clinically stable multiple sclerosis supports the concept that multiple sclerosis is associated with ongoing proteolysis that may result in progressive tissue damage. The selective inhibition of MMP-9 could be a useful approach for the prevention of disease progression in multiple sclerosis.

Reversion-inducing cysteine-rich protein with kazal motifs and matrix metalloproteinase-9 are prognostic markers in skull base chordomas

“…[12] Whether this theory is applicable or not in skull base chordoma and whether expression of MMP will increase with increased number of surgeries will need further study.…”

“…In astrocytic tumor, meningiomas, pituitary adenomas, multiple sclerosis, and meningitis they were proven to be significant increased of matrix metalloproteinases expression. [9,10,11,12,13,18] In skull base chordomas, there is only one report mentioning about MMP expression.…”

Identification of a Matrix-Degrading Phenotype in Human Tuberculosis In Vitro and In Vivo

“…MMP-9 is not normally present in cerebrospinal fluid (CSF), but has been detected in patients with Lyme disease (11), viral meningitis (12), human T cell lymphotrophic virus-1-associated myelopathy (13), and multiple sclerosis (14,15). MMP-9 was detected in 40% of patients with HIV infection and more commonly in cases with neurological deficit (16).…”

“…TIMP-1 binds to the active and latent forms of MMP-9 and is the major TIMP secreted by mononuclear phagocytes (27). It is constitutively secreted into many tissue fluids, including CSF (14,17), and the balance between the local TIMP-1 and MMP-9 concentrations critically determines net proteolytic activity.…”

Tissue Inhibitor of Metalloproteinase-1 Prevents Cytokine-Mediated Dysfunction and Cytotoxicity in Pancreatic Islets and β-cells

“…The obvious need for a dynamic process that regulates collagen turnover is evident in wound repair and remodeling (2,3). However, MMPs and TIMPs are involved in other significant but less obvious processes, such as tumor invasion and metastasis (4 -7), inflammatory responses (8), embryonic development (9,10), arthritic diseases (11,12), and multiple sclerosis (13,14).…”