Increased expression ratio of matrix metalloproteinase-9 (MMP9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) RNA levels in Iranian multiple sclerosis patients.
OBJECTIVE
Multiple sclerosis (MS) is an autoimmune disease involving the central nervous system (CNS) with unknown immunopathogenic mechanisms. Matrix metalloproteinase-9 (MMP-9) facilitates T-cell migration into the CNS while the tissue inhibitor matrix metalloproteinase-1 (TIMP-1) inhibits MMP-9 actions. The aim of this study was to evaluate the expression of TIMP-1 RNA and MMP-9/TIMP-1 RNA ratio in blood cells of Iranian patients with relapsing-remitting multiple sclerosis (RRMS) treated with IFNb.


METHODS
The study compared the expression level of TIMP-1 gene in RRMS samples with normal individuals in Iran and the results were compared using a ratio of MMP-9 to TIMP-1. All patients were HLA-DRB1*15 negative and were responders to interferon-beta with a normal vitamin D level.


RESULTS
The RRMS patients manifested a lower expression level of TIMP-1 RNA than their normal counterparts although the result was not significant (P= 0.06). Also, the ratio of MMP-9 to TIMP-1 RNA increased significantly (P= 0.009). There was no linear correlation between TIMP-1 expression level and risk of Expanded Disability Status Scale of Kurtzke (EDSS); nor was there any significant correlation between expression status of TIMP-1 and duration of the disease. Although there was no significant decrease in TIMP-1 expression level, the MMP-9/TIMP-1 RNA ratio in RRMS was significantly higher than normal subjects.


CONCLUSIONS
Further studies are recommended to compare MMP-9/TIMP-1 RNA ratio in patients before and after taking IFN-beta in order to find out if MMP-9/TIMP-1 RNA ratio can function as a proper marker of the bio efficacy of IFN-beta treatment of MS.
Department of Biology, Tonekabon Branch, Islamic Azad University, Tonekabon, Tonekabon, Iran.|Department of Biology, Tonekabon Branch, Islamic Azad University, Tonekabon, Tonekabon, Iran.
Marzieh Khoshbin
MK
Nazdik
Department of Medical Genetics, School of Medicine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Department of Biology, Tonekabon Branch, Islamic Azad University, Tonekabon, Tonekabon, Iran.
Mohammad
M
Taheri
Department of Hematology, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Elham
E
Sajjadi
Department of Epidemiology and Biostatistics, Faculty of Health, Qom University of Medical Sciences, Qom, Iran.
Shahram
S
Arsang-Jang
Department of Biology, Tonekabon Branch, Islamic Azad University, Tonekabon, Tonekabon, Iran.
Zeinab Kazaei
ZK
Koohpar
GenoDive Pharma Inc., Atsugi, Japan.
Hidetoshi
H
Inoko
Department of Medical Genetics, School of Medicine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Arezou
A
Sayad
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics* / Q000276:immunology; D014807:Vitamin D / Q000097:blood
D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen; D007155:Immunologic Factors; D012333:RNA, Messenger; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D014807:Vitamin D; D016899:Interferon-beta; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
MMP-9; TIMP-1; expression; multiple sclerosis; real time PCR