Rezapour-Firouzi Soheila, Shahabi Shahram, Mohammadzadeh Adel, Tehrani Ali Asgar, Kheradmand Fatemeh, Mazloomi Ebrahim
Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, I.R. Iran.
Departement of Immunology and Genetics, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, I.R. Iran.
Res Pharm Sci. 2018 Dec;13(6):523-532. doi: 10.4103/1735-5362.245964.
The mammalian target of rapamycin (mTOR) has a fundamental role in the metabolism, growth, and regulation of the immune system. The interferon gamma (IFN-γ)derived from T helper 1 (Th1) cells is a prominent pro-inflammatory cytokine in multiple sclerosis (MS) and its animal model, the experimental autoimmune encephalomyelitis (EAE). Due to the exclusive role of rapamycin (RAPA) in mTOR complex 1 (mTORC1) inhibition, essentially Th1 differentiation and IFN-γ production, we evaluated the potential therapeutic effects of hemp seed/evening primrose oils (HSO/EPO) in comparison with RAPA administration in EAE. To evaluate the therapeutic effects of EPO/HSO supplement in comparison with RAPA, EAE was induced using myelin oligodendrocyte glycoprotein (MOG) peptide and complete Freund's adjuvant in C57BL/6 mice. The weight, clinical score, and histological findings were evaluated. Total mRNA was extracted from local lymph nodes and qRT-PCR was used for the purpose of the genes expression level of regulatory associated protein of TORC1 () and IFN-γ. Our results indicated that the relative expression of and -γ genes were significantly reduced in HSO/EPO, RAPA, and RAPA + HSO/EPO treated groups in comparison with the untreated group. Interestingly, histological findings have shown that the HSO/EPO treated group remarkably regenerated the myelin sheath, but this did not occur in the case of RAPA or combined RAPA and HSO/EPO treated groups. Our findings suggeste that HSO/HPO can be used as a potent immunomodulator and as a good candidate for re-myelination and downregulation of immune response for treatment of MS.
雷帕霉素的哺乳动物靶点(mTOR)在免疫系统的代谢、生长和调节中具有重要作用。源自辅助性T细胞1(Th1)的干扰素γ(IFN-γ)是多发性硬化症(MS)及其动物模型实验性自身免疫性脑脊髓炎(EAE)中一种突出的促炎细胞因子。由于雷帕霉素(RAPA)在抑制mTOR复合物1(mTORC1)方面具有独特作用,本质上是抑制Th1分化和IFN-γ产生,我们评估了大麻籽/月见草油(HSO/EPO)与RAPA给药相比在EAE中的潜在治疗效果。为了评估EPO/HSO补充剂与RAPA相比的治疗效果,在C57BL/6小鼠中使用髓鞘少突胶质细胞糖蛋白(MOG)肽和完全弗氏佐剂诱导EAE。评估了体重、临床评分和组织学结果。从局部淋巴结提取总mRNA,并使用qRT-PCR检测TORC1调节相关蛋白()和IFN-γ的基因表达水平。我们的结果表明,与未治疗组相比,HSO/EPO、RAPA和RAPA + HSO/EPO治疗组中 和 -γ基因的相对表达显著降低。有趣的是,组织学结果表明,HSO/EPO治疗组的髓鞘显著再生,但RAPA或RAPA与HSO/EPO联合治疗组则未出现这种情况。我们的研究结果表明,HSO/HPO可作为一种有效的免疫调节剂,是用于MS治疗的髓鞘再生和下调免疫反应的良好候选物。