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The Role of Β-D-Mannuronic Acid, As a New Non-Steroidal Anti-Inflammatory Drug on Expression of Mir-146A, Irak1, Traf6, Nf-Κb and Pro-Inflammatory Cytokines Following a Clinical Trial in Rheumatoid Arthritis Patients Publisher Pubmed



Mortazavijahromi SS1 ; Ahmadzadeh A2 ; Rezaieyazdi Z3 ; Aslani M1 ; Omidian S1 ; 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. Department of Rheumatology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Source: Immunopharmacology and Immunotoxicology Published:2020


Abstract

Context: miR-146a, its targets (IRAK1, TRAF6) and NF-κB transcription factor play a fundamental role in rheumatoid arthritis (RA). Positive effects of drug β-d-mannuronic acid (M2000) were proven on their expression in the HEK-Blue hTLR2 cell line, and results of its phase III clinical trial on RA patients were encouraging. Objective: This research aimed to investigate the effects of M2000 on expression of these genes and serum levels of IL-6 and TNF-α as pro-inflammatory cytokines in RA patients. Material and methods: In this study (Trial Registration Number: IRCT2017100213739N10), 12 RA patients (according to the American College of Rheumatology criteria) and 12 healthy subjects (as control group) were selected. The gene expression of miR-146a, IRAK1, TRAF6, and NF-κB were measured at the baseline and after 12 weeks M2000 therapy, using quantitative real-time PCR method. Moreover, the serum levels of IL-6 and TNF-α were evaluated at the similar times by ELISA method. Results: Our findings showed that the gene expression of miR-146a, IRAK1, TRAF6, and NF-κB significantly decreased after 12 weeks M2000 therapy in RA patients (0.81-, 0.68-, 0.79-, 0.82-fold, with p <.05, p <.01, p <.01, p <.05, respectively). Furthermore, the serum levels of IL-6 and TNF-α significantly reduced in these patients after 12 weeks M2000 therapy (both with p <.05). Conclusions: The present research results determined the part of molecular mechanisms of drug M2000 in RA treatment, based on the expression and function modification of miR-146a, IRAK1, TRAF6, NF-κB, IL-6 and TNF-α. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
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