| A Novel Combination of Docosahexaenoic Acid, All-Trans
Retinoic Acid, and 1, 25-Dihydroxyvitamin D3 Reduces 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 alltrans 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. |