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The Immunomodulatory Effects of All-Trans Retinoic Acid and Docosahexaenoic Acid Combination Treatment on the Expression of Il-2, Il-4, T-Bet, and Gata3 Genes in Pbmcs of Multiple Sclerosis Patients Publisher Pubmed



Naslkhameneh AM1 ; Mirshafiey A2 ; Moghadasi AN3 ; Yekaninejad MS4 ; Parastouei K5 ; Nejati S6 ; Sabooryaraghi AA1, 2
Authors
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Authors Affiliations
  1. 1. Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, International Campus, Tehran, Iran
  2. 2. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Neurology and MS Research Center, Neuroscience Institute, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Immunology, School of Medicine, Babol University of Medical Sciences, Babol, Iran

Source: Neurological Research Published:2023


Abstract

Objectives: Multiple sclerosis (MS) is a potentially disabling autoimmune disease of the central nervous system. Neither the pathogenesis nor the effectiveness of treatment of MS has been fully understood. This in vitro trial evaluated the beneficial immunomodulatory effects of single and combined treatments of all-trans retinoic acid (ATRA) and docosahexaenoic acid (DHA) on the peripheral blood mononuclear cells (PBMCs) of relapsing-remitting MS (RRMS) patients who were receiving interferon beta (IFN-β). Methods: The PBMCs of 15 RRMS patients were isolated, cultured, and treated with single and combined treatments of ATRA and DHA. The expressions of IL-2, IL-4, T-bet, and GATA3 genes were evaluated using real-time PCR. Results: The results showed that a single treatment of ATRA could significantly suppress the gene expression of the pro-inflammatory cytokine, IL-2 (P < 0.05), and related transcription factor, T-bet (P < 0.001). The gene expression level of the anti-inflammatory cytokine, IL-4, and its transcription factor, GATA3, were not significantly changed. The expression of IL-2 and T-bet genes was significantly decreased in combination treatments of ATRA and DHA (P < 0.001). Significant suppression of IL-2 and T-bet (P < 0.001) was observed in ATRA and DHA combination therapy with half doses of their single treatment, which suggested a synergistic effect of these components. Discussion: Co-administration of vitamin A and DHA, an omega-3 fatty acid derivative, may exert a synergistic effect in modulating the immune system in MS patients; however, more studies are needed to evaluate the exact effects and mechanism of their actions on the immune cells. © 2023 Informa UK Limited, trading as Taylor & Francis Group.
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