Increased expression ratio of matrix metalloproteinase-9 (MMP9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) RNA levels in Iranian multiple sclerosis patients

Hum Antibodies. 2016;24(3-4):65-70. doi: 10.3233/HAB-160296.

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.

Keywords: MMP-9; TIMP-1; expression; multiple sclerosis; real time PCR.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Gene Expression Regulation
  • HLA-DRB1 Chains / genetics
  • HLA-DRB1 Chains / immunology
  • Humans
  • Immunologic Factors / therapeutic use
  • Interferon-beta / therapeutic use
  • Male
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / immunology
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / genetics*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • RNA, Messenger / genetics*
  • RNA, Messenger / immunology
  • Real-Time Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-1 / genetics*
  • Tissue Inhibitor of Metalloproteinase-1 / immunology
  • Vitamin D / blood

Substances

  • HLA-DRB1 Chains
  • HLA-DRB1*15 antigen
  • Immunologic Factors
  • RNA, Messenger
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Vitamin D
  • Interferon-beta
  • MMP9 protein, human
  • Matrix Metalloproteinase 9