Mousavi Nasl-Khameneh Ateke, Mirshafiey Abbas, Naser Moghadasi Abdorreza, Chahardoli Reza, Mahmoudi Maryam, Parastouei Karim, Yekaninejad Mir Saeed, Saboor-Yaraghi Ali Akbar
a Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, International Campus , Tehran University of Medical Sciences , Tehran , Iran.
b Department of Immunology, School of Public Health , Tehran University of Medical Sciences , Tehran , Iran.
Neurol Res. 2018 Jan;40(1):11-17. doi: 10.1080/01616412.2017.1382800. Epub 2017 Nov 18.
Multiple sclerosis (MS) is a demyelinating disorder with a complex autoimmune pathophysiology. Its initiation and progression correlate with IL-17 and the related transcription factor, RORγt. All-trans retinoic acid (ATRA) is a bioactive derivative of vitamin A, and docosahexaenoic acid (DHA) is an active metabolite of omega-3 fatty acid; both have immunomodulatory effects in many immune disorders. This study investigated the effects of DHA and ATRA individually and in combination on IL-17 and RORγt gene expression in peripheral blood mononuclear cells (PBMCs) of relapsing-remitting MS (RRMS) patients who were receiving interferon beta (IFN-β).
The PBMCs of 15 RRMS patients were treated in vitro with 1 μM of ATRA and 15 μM of DHA as single and combination treatments for assessing probable additive or synergistic effects.
The results showed that single treatment of ATRA (p = 0.05) could significantly decrease the expression of IL-17 gene and single treatment of ATRA (p = 0.04) and single treatment of DHA (p = 0.05) induced significant inhibition on the expression of RORγt gene. The suppressive effect of combined treatment with ATRA and DHA on IL-17 (p = 0.02) and RORγt (p = 0.01) was also found significant showing that the combined treatments can have additive effects.
These results indicate that both DHA and ATRA might help control disease progression in IFN-β treated RRMS patients with the strongest effects produced by a combination of the two compounds.
多发性硬化症（MS）是一种具有复杂自身免疫病理生理学的脱髓鞘疾病。其发病和进展与白细胞介素-17（IL-17）及相关转录因子维甲酸相关孤儿受体γt（RORγt）相关。全反式维甲酸（ATRA）是维生素A的生物活性衍生物，二十二碳六烯酸（DHA）是ω-3脂肪酸的活性代谢产物；二者在许多免疫疾病中均具有免疫调节作用。本研究调查了DHA和ATRA单独及联合使用对正在接受β-干扰素（IFN-β）治疗的复发缓解型多发性硬化症（RRMS）患者外周血单个核细胞（PBMC）中IL-17和RORγt基因表达的影响。
将15例RRMS患者的PBMC在体外分别用1μM ATRA和15μM DHA进行单一及联合处理，以评估可能的相加或协同作用。
结果显示，单独使用ATRA处理（p = 0.05）可显著降低IL-17基因的表达，单独使用ATRA处理（p = 0.04）和单独使用DHA处理（p = 0.05）均能显著抑制RORγt基因的表达。ATRA与DHA联合处理对IL-17（p = 0.02）和RORγt（p = 0.01）的抑制作用也很显著，表明联合处理具有相加效应。
这些结果表明，DHA和ATRA可能有助于控制接受IFN-β治疗的RRMS患者的疾病进展，二者联合使用产生的效果最强。
