title: A Novel Combination of Docosahexaenoic Acid, All-Trans Retinoic Acid, and 1, 25-Dihydroxyvitamin D3Reduces T-Bet Gene Expression, Serum Interferon Gamma, and Clinical Scores but Promotes PPARγ Gene Expression in Experimental Autoimmune Encephalomyelitis.
abstract: 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 D3(D3), 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, D3, 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 γ secretion in serum and T-bet mRNA expression in splenocytes were significantly reduced (p = 0.004, p = 0.029, respectively) while PPARγ mRNA expression was significantly increased in Group T compared to Group E (p = 0.021). These findings highlighted that ATRA, D3, and DHA combination modulated PPARγ 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.
authors.affiliation: Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, International Campus, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Shiri-Shahsavar
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Mirshafiee
authors.affiliation: Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Karim
authors.initials: K
authors.lastname: Parastouei
authors.affiliation: Neuroscience Department, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Ebrahimi-Kalan
authors.affiliation: Department of Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Yekaninejad
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farid
authors.initials: F
authors.lastname: Soleymani
authors.affiliation: Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Chahardoli
authors.affiliation: Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ramin
authors.initials: R
authors.lastname: Mazaheri Nezhad Fard
authors.affiliation: Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, International Campus, Tehran University of Medical Sciences, Tehran, Iran. asaboor@tums.ac.ir.|Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. asaboor@tums.ac.ir.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Saboor-Yaraghi
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004338:Drug Combinations; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014815:Vitamins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000098815:T-bet Transcription Factor
chemical_list: D004338:Drug Combinations; D047495:PPAR gamma; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014815:Vitamins; D004281:Docosahexaenoic Acids; D014212:Tretinoin; D007371:Interferon-gamma; D002117:Calcitriol
keywords: ATRA, D3 and DHA combination therapy; Experimental autoimmune encephalomyelitis (EAE); Multiple sclerosis (MS); Peroxisome proliferator-activated receptor gamma (PPARγ); T-bet; Vitamins