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The Potent Suppressive Effect of Β-D-Mannuronic Acid (M2000) on Molecular Expression of the Tlr/Nf-Kb Signaling Pathway in Ankylosing Spondylitis Patients Publisher Pubmed



Roozbehkia M1 ; Mahmoudi M2 ; Aletaha S1 ; Rezaei N3 ; Fattahi MJ1 ; Jafarnezhadansariha F1 ; Barati A1 ; 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. Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran
  3. 3. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Sheffield, United Kingdom

Source: International Immunopharmacology Published:2017


Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized by the inflammation of sacroiliac joints and axial skeleton. A combination of genetic, environmental and immunological factors are involved in AS's pathogenesis. TLRs are type I transmembrane glycoproteins that play a crucial role in the innate immune responses against invading pathogens. Observational studies have demonstrated a possible association between TLR dysregulation and AS. The β-D-mannuronic acid (M2000), as a novel NSAID with immunosuppressive property, has shown an inhibitory effect on Toll-like receptor (TLR) 2, 4 signaling in HEK293 cells. In the present study, we investigated the gene expression of Myd88, IKB-alpha, NF-kB and MAPK14 (genes of the TLR/NF-kB Signaling Pathway) in AS patients in comparison to healthy subjects and also the effect of β-D-mannuronic acid on disease activity and mRNA expression of these molecules in affected patients. We showed for the first time that the gene expression level of Myd88, IKB-alpha, NF-kB and MAPK14 was higher in AS patients in comparison to healthy subjects. Moreover we confirmed that the β-D-mannuronic acid not just reduced significantly the disease activity of AS individuals compared to placebo, but also it could significantly decrease the expression level of genes associated with TLR/NF-kB Signaling Pathway in treated patients with M2000. These results may provide a new therapeutic approach to attenuate inflammatory responses in AS patients, (Identified; IRCT 2013062213739 N1). © 2017
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