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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

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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