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Effect of Guluronic Acid (G2013), As a New Anti-Inflammatory Drug on Gene Expression of Pro-Inflammatory and Anti-Inflammatory Cytokines and Their Transcription Factors in Rheumatoid Arthritis Patients Publisher Pubmed



Bakhtiari T1 ; Azarian S1 ; Ghaderi A2 ; Ahmadzadeh A3 ; Mirshafiey A1, 4
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, P.O.Box: 14155-6446, Tehran, Iran
  2. 2. Department of Internal Medicine, Hematology and Medical Oncology Ward, Cancer Research Centre, Cancer Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Rheumatology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Research Centre for Immunodeficiencies, Children's Medical Centre, Tehran University of Medical Sciences, Tehran, Iran

Source: Iranian Journal of Allergy# Asthma and Immunology Published:2019


Abstract

Rheumatoid arthritis (RA) as a long-term autoimmune disease is characterized by pain, swelling and joints destruction. The therapeutic efficacy of Guluronic acid (G2013) (patented, DEU: 102016113017.6) was reported in phase I/II clinical trial in RA patients. In this study, we aimed to evaluate the effect of G2013 as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive property on genes expression of anti-inflammatory and pro-inflammatory cytokines and their transcription factors in the blood sample of RA patients. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments which were disease-modifying anti-rheumatic drugs (DMARDs), NSAID, and biologics. G2013 was administered orally at a dose of 500 mg twice daily for 12 weeks. Before and after the treatment of patients with drug G2013, the peripheral blood mononuclear cells (PBMCs) were isolated for evaluating the gene expression level of interleukin 10 (IL10), interleukin 22 (IL22), interferon γ (IFNγ), and transcription factors specific to the T helper cell lineages, forkhead box P3 (Fox-P3), Aryl hydrocarbon receptor (AHR) and T-box–containing protein expressed in T cells (T-bet) using the real-time PCR method. Since these cytokines have a key role in the progression of RA and disease condition expected induction of IFNγ, AHR, IL22, T-bet, and reduction of IL10, Fox-P3. Results indicated a significant reduction in the level of IFNγ, AHR and a significant induction in IL10, Fox-P3 gene expression in comparison with the control group. In conclusion; the results of this investigation showed a part of the immunological mechanism of G2013 as a novel anti-inflammatory that could reduce pro-inflammatory cytokine and their transcription factors. Furthermore, it increased the anti-inflammatory cytokine and its transcription factor (clinical trial identifier: IRCT2016092813739N5). Copyright© December 2019, Iran J Allergy Asthma Immunol. All rights reserved.
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