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

• Published in: Immunopharmacology and immunotoxicology Vol. 42; no. 3; pp. 228 - 236
• Main Authors: Mortazavi-Jahromi, Seyed Shahabeddin, Ahmadzadeh, Arman, Rezaieyazdi, Zahra, Aslani, Mona, Omidian, Saiedeh, Mirshafiey, Abbas
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.05.2020
• Subjects: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Cytokines - blood; Female; Hexuronic Acids - therapeutic use; Humans; Interleukin-1 Receptor-Associated Kinases - genetics; Interleukin-6 - blood; Intracellular Signaling Peptides and Proteins - genetics; M2000; Male; MicroRNAs - genetics; Middle Aged; miR-146a; NF-kappa B - genetics; NSAID; rheumatoid arthritis; target molecules (IRAK1; TRAF6; Treatment Outcome; Tumor Necrosis Factor-alpha - blood; Young Adult; β-d-mannuronic acid; β-d-mannuronic acid; NSAID; TRAF6; target molecules (IRAK1; miR-146a; rheumatoid arthritis; M2000
• ISSN: 0892-3973; 1532-2513; 1532-2513
• DOI: 10.1080/08923973.2020.1742734

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.