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The Effects of Mannuronic Acid on Il-1Β, Il-17A, Stat1, and Stat3 Gene Expressions and Tlr2 and Tlr4 Molecules in Multiple Sclerosis Publisher Pubmed



Najafi S1 ; Saadat P2 ; Beladi Moghadam N3 ; Manoucherinia A4 ; Aghazadeh Z1 ; Vali Mohammadi A5 ; Noorbakhsh SM1 ; Movahedi M6 ; Nikouei Moghaddam MR6 ; Pashaiefar H7 ; Mirshafiey A1
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Mobility Impairment Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  3. 3. Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
  4. 4. Department of Clinical Neuroscience (CNS), Karolinska Institutet, Stockholm, Sweden
  5. 5. Shiraz Branch, Islamic Azad University, Shiraz, Iran
  6. 6. Department of Biochemistry, Faculty of Life Sciences, Tehran North Branch, Islamic Azad University, Tehran, Iran
  7. 7. Hematology, Oncology and Stem cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran

Source: Journal of Clinical Pharmacology Published:2022


Abstract

Multiple sclerosis (MS) is a chronic neurologic disease defined by inflammation and demyelination of the central nervous system that comes with variable degrees of axonal and neuronal damage. The efficacy of β-D-mannuronic acid (M2000) as a novel drug with immunosuppressive properties (patented: PCT/EP2017/067920), has been shown in an experimental model of MS. In this study, the effects of M2000 on interleukin (IL)-1β, IL-17A, signal transducer and activator of transcription (STAT) 1, and STAT3 gene expressions and Toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) molecules in patients with secondary progressive MS were evaluated. In this study, 14 patients with secondary progressive MS and 14 healthy subjects (as control group) were entered from the phase 2 clinical trial (Clinical Trial identifier, IRCT2016111313739N6). The gene expressions of IL-1β, IL-17A, STAT1, and STAT3 were assessed at the baseline and then measured after 6 months of therapy with M2000 by using the quantitative real-time polymerase chain reaction method. Moreover, the expressions of TLR2 and TLR4 molecules on peripheral blood mononuclear cells were evaluated by the flow cytometry method. The gene expressions of IL-17A, STAT1, and STAT3 in patients with MS decreased after 6 months of therapy with M2000 comparing before treatment. Also, the gene expression of IL-1β decreased numerically after 6 months. Furthermore, the expressions of TLR2 and TLR4 on PBMCs of the patients declined when compared to baseline. The results of this investigation revealed that M2000 could downregulate IL-17, STAT1, and STAT3 genes in patients with secondary progressive MS and also reduce the expressions of TLR2 and TLR4 on PBMCs. Moreover, M2000 declined numerically IL-β gene expression. © 2021, The American College of Clinical Pharmacology.
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