Serum MMP-2 and MMP-9 are elevated in different multiple sclerosis subtypes.
In multiple sclerosis (MS), matrix metalloproteinase (MMP) activity in tissues is the result of a balance between MMPs and their tissue inhibitors (TIMPs). MMP-9 predominates in acute MS lesions and is inhibited by TIMP-1, while MMP-2 may participate in the remodeling of the extracellular matrix (ECM) such as in chronic disease and is inhibited by TIMP-2. These differences may be reflected in serum and cerebrospinal fluid (CSF). We have tried to characterize MMP-2 and MMP-9 activities, in relation to their respective TIMPs, 2 and 1, as a factor of different types of the disease, as this information was not previously clearly stated. We found the MMP-2/TIMP-2 ratio in serum to show higher values in secondary progressive (SP, p=0.02) and primary progressive (PP, p=0.01) MS than short disease duration (SDD) relapsing-remitting (RR) MS, but not different from the healthy control (HC) group. Whereas the MMP-9/TIMP-1 ratio in serum showed higher (p=0.04) values in SDD RR MS than PP but also in active patients, evaluated either clinically (p=0.006) or from the magnetic resonance imaging (MRI, p<0.05), compared to inactive disease. CSF MMP to TIMP ratios did not differ between MS subtypes, suggesting systemic rather CNS-restricted changes. These results show that an increase in MMP-2/TIMP-2 ratio marks chronic progression in MS, but it is as high as in HC, and also confirm that high MMP-9 activity characterizes short duration relapsing and active forms of the disease.
Avolio
Carlo
C
Neurology Unit, University of Foggia, Italy.
Ruggieri
Maddalena
M
Giuliani
Fabrizio
F
Liuzzi
Grazia Maria
GM
Leante
Rosaria
R
Riccio
Paolo
P
Livrea
Paolo
P
Trojano
Maria
M
D000328:Adult; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood* / Q000276:immunology*; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000276:immunology*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000276:immunology*; D009413:Nerve Fibers, Myelinated / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000276:immunology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology*
D007074:Immunoglobulin G; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9