Marzieh Khoshbin Nazdik1,1, Mohammad Taheri2,1, Elham Sajjadi3, Shahram Arsang-Jang4, Zeinab Kazaei Koohpar1, Hidetoshi Inoko5, Arezou Sayad2. 1. Department of Biology, Tonekabon Branch, Islamic Azad University, Tonekabon, Tonekabon, Iran. 2. Department of Medical Genetics, School of Medicine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Department of Hematology, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Department of Epidemiology and Biostatistics, Faculty of Health, Qom University of Medical Sciences, Qom, Iran. 5. GenoDive Pharma Inc., Atsugi, Japan.
Abstract
OBJECTIVES: 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. MATERIAL AND 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. CONCLUSION: 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.
OBJECTIVES: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. MATERIAL AND 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. CONCLUSION: 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.
Entities:
Keywords:
MMP-9; TIMP-1; expression; multiple sclerosis; real time PCR