RESUMO
Multiple Sclerosis (MS) is a chronic inflammatory disease that leads to degeneration of the brain and spinal tissue. Imbalances of CD4+ T cells including Thelper1 (Th1)/Thelper2 (Th2) and Thelper17 (Th17)/Tregulatory (Treg), their secreted cytokines and gene expressions, are important aspects of in immunopathogenesis of MS. Vitamin A and its metabolites can regulate the immune system and appears to be effective in preventing progression of the autoimmune disease such as MS. Disease progression was evaluated By Magnetic Resonance Imaging (MRI), Expanded Disability States Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) tests. Cytokine levels were measured using ELISA kits and gene expression was quantified by Real time PCR (RT-PCR) system. According to the difference between the epidemiological and clinical data on the relationship between vitamin A and immune system regulation, this study of the first time assesses Immune function as well as gene expression and progression of the disease following administration of vitamin A supplement.
Assuntos
Citocinas/metabolismo , Regulação da Expressão Gênica , Esclerose Múltipla/patologia , Vitamina A/administração & dosagem , Progressão da Doença , Método Duplo-Cego , Humanos , Esclerose Múltipla/genética , Esclerose Múltipla/metabolismo , Placebos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Vitamin A and its derivatives have been shown to modulate the immune system via retinoic acid receptor (RAR). This study explored the impact of retinyl palmitate supplementation on RAR subtype gene expression in peripheral blood mononuclear cells (PBMCs) in multiple sclerosis (MS) patients. The study designed as a double-blind randomized clinical trial in which relapsing remitting multiple sclerosis patients were evaluated. Both groups received one capsule 50,000 IU vitamin D3 per 2 weeks and one intramuscular injection interferon beta-1a per week. The intervention group received one 25,000 IU retinyl palmitate capsule daily for 6 months and the placebo group received one placebo capsule daily. The PBMCs were isolated from participants and the expression level changes of RAR-α and RAR-γ genes were determined by real-time PCR. After supplementation, in the intervention group, the RAR-α gene expression level was significantly decreased compared to the placebo group (p = 0.03); however, the expression of RAR-γ gene did not significantly change (p = 0.10). These results show that vitamin A supplementation can significantly downregulate the expression of RAR-α gene in PBMCs of MS patients that suggest the presence of in vivo regulatory mechanisms for the action of vitamin A on the immune system.
Assuntos
Suplementos Nutricionais , Esclerose Múltipla/metabolismo , Receptores do Ácido Retinoico/genética , Vitamina A/farmacologia , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Receptores do Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico , Transcrição Gênica/efeitos dos fármacos , Vitamina A/administração & dosagem , Receptor gama de Ácido RetinoicoRESUMO
The aim of this study was to investigate the role of vitamin A on RORγt and IL-17 gene expression in multiple sclerotic patients. Patients in the vitamin A group received 25,000 IU retinyl palmitate per day, while patients in the placebo group took one capsule of placebo per day for 6 months. Gene expression was measured by real-time PCR at the first and end of the study. The results of this study show that vitamin A downregulates IL-17 and RORγt gene expression. No changes in gene expression occurred in the placebo group.
Assuntos
Interleucina-17/metabolismo , Esclerose Múltipla/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Vitamina A/farmacologia , Vitaminas/farmacologia , Adulto , Regulação para Baixo , Feminino , Humanos , Interferon beta-1a , Interferon beta/uso terapêutico , Interleucina-17/genética , Masculino , Esclerose Múltipla/tratamento farmacológico , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Transcrição Gênica/efeitos dos fármacos , Vitamina A/administração & dosagem , Vitaminas/administração & dosagemRESUMO
Myelin oligodendrocyte glycoprotein (MOG) is one of the autoantigens used in evaluation of the CD4(+) T cells proliferation response in multiple sclerotic patients. In cell culture, human serum (HS) is one of the promising substitutions for fetal calf serum (FCS) that can induce different autoreactivity of T cells and fluctuation of autoantibody production from B cells. Because of immunomodulatory function of vitamin A, we examined the effect of HS and FCS on CD4(+) T cells proliferation in response to MOG in correlation with serum retinol-binding protein (RBP)/transthyretin (TTR) ratio, as an indirect way to assess vitamin A status in multiple sclerotic patients. Patients' peripheral blood mononuclear cells were isolated and cultured in the presence of MOG as well as FCS and HS both separately and together. Cell proliferation was evaluated using BrdU kit. Serum RBP and TTR levels were measured by ELISA kit. FCS and HS increase CD4(+) T cell proliferation. RBP/TTR ratio has significant negative correlation with cell proliferation in the presence of MOG, HS, and FCS. HS with FCS provides an appropriate medium for autoreactivity and proliferation of CD4(+) T cells. Vitamin A has a crucial role in regulation of this pathway.
