A Novel Combination of Docosahexaenoic Acid, All-Trans Retinoic Acid, and 1, 25-Dihydroxyvitamin D-3 Reduces T-Bet Gene Expression, Serum Interferon Gamma, and Clinical Scores but Promotes PPAR gamma Gene Expression in Experimental Autoimmune Encephalomyelitis

作者：Shiri Shahsavar Mohammad Reza; Mirshafiee Abbas; Parastouei Karim; Ebrahimi Kalan Abbas; Yekaninejad Saeed; Soleymani Farid; Chahardoli Reza; Fard Ramin Mazaheri Nezhad; Saboor Yaraghi Ali Akbar^*

来源：Journal of Molecular Neuroscience, 2016, 60(4): 498-508.

DOI：10.1007/s12031-016-0834-4

• Multiple sclerosis (MS)
• Experimental autoimmune encephalomyelitis (EAE)
• Peroxisome proliferator-activated receptor gamma (PPAR gamma)
• Vitamins
• T-bet
• ATRA
• D-3 and DHA combination therapy

Vitamins are immunologically interesting due to their significant immunomodulatory activities. Experimental autoimmune encephalomyelitis (EAE) is one of the most commonly used experimental models for studying autoimmune disorder in multiple sclerosis (MS). The aim of this study was to evaluate the protective and ameliorative effects of novel combination of all-trans retinoic acid (ATRA), 1,25-dihydroxyvitamin D-3 (D-3), and docosahexaenoic acid (DHA) on EAE-specific determinants and target gene expressions. Mice were randomly categorized into three groups before EAE induction [non-treated EAE (Group E), treated EAE (Group T), and healthy mice (Group H)]. Encephalomyelitis was induced in female C57BL/6 mice by subcutaneous immunization using commercial kits. Preceding day of EAE induction, combination of ATRA, D-3, and DHA was administered with a single IP injection every 48 h and continued until day 26. Findings of present study showed that administration of vitamins A, D, and DHA significantly decreased average clinical scores, cumulative EAE score, and EAE incidence in Group T, compared to Group E (p values < 0.001). Interferon gamma secretion in serum and T-bet mRNA expression in splenocytes were significantly reduced (p = 0.004, p = 0.029, respectively) while PPAR gamma mRNA expression was significantly increased in Group T compared to Group E (p = 0.021). These findings highlighted that ATRA, D-3, and DHA combination modulated PPAR gamma and T-bet gene expression and resulted in decrease in Th1 response and lymphocyte invasion into the central nervous system (CNS) and resultant inflammation. In conclusion, the results of this study suggested the potential use of this intervention in treatment and/or prevention of EAE/MS and probably other Th1 cell-mediated autoimmune diseases.

• 出版日期2016-12