Regulatory effects of hemp seed/evening primrose oil supplement in comparison with rapamycin on the expression of the mammalian target of rapamycin-complex 2 and interleukin-10 genes in experimental autoimmune encephalomyelitis

Soheila Rezapour-Firouzi , Fatemeh kheradmand, Shahram Shahabi, Ali Asghar Tehrani, Ebrahim Mazloomi, Adel Mohammadzadeh

Abstract


The mammalian target of rapamycin (mTOR) signaling plays a critical role in lipid synthesis and immune responses. The T regulatory cells (Treg) as suppressor of T cells, are a subset of T cells that modulate the immune system, maintain tolerance, and prevent autoimmune diseases.. The interleukin (IL) -10 derived from the Treg and T helper (Th) 2 is an anti-inflammatory cytokine in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Due to the exclusive roles of rapamycin (RAPA) in mTOR inhibition, we evaluated the regulatory effect of the hemp seed oil/evening primrose oil (HSO/EPO) supplement in comparison with RAPA in EAE. EAE was induced by using myelin oligodendrocyte glycoprotein peptide and complete freund's adjuvant (CFA) in C57BL/6 mice, total mRNA was extracted from local lymph nodes and real-time polymerase chain reaction was used to evaluate the expression level of the rapamycin-insensitive companion of mTOR complex 2 (RICTOR) and IL-10 genes. The expression of IL-10 and RICTOR genes were significantly increased in HSO/EPO group. In contrast with RAPA groups, histological findings have shown that the HSO/EPO treated group remarkably reduced cell infiltration and promoted remyelination. The EPO/HSO has beneficial effects on the repair of myelin, which was confirmed by immunological and histological findings.


Keywords


Autoimmune encephalomyelitis; Demyelination; Immune tolerance; Lymph node; Rapamycin.

Full Text:

PDF

References


Dazert E, Hall MN. mTOR signaling in disease. Curr Opin Cell Biol. 2011;23(6):744-755.

Lisi L, Navarra P, Cirocchi R, Sharp A, Stigliano E, Feinstein DL, et al. Rapamycin reduces clinical signs and neuropathic pain in a chronic model of experimental autoimmune encephalomyelitis. J Neuroimmunol. 2012;243(1-2):43-51.

Bettelli E, Das MP, Howard ED, Weiner HL, Sobel RA, Kuchroo VK. IL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10- and IL-4-deficient and transgenic mice. J Immunol. 1998;161(7):3299-3306.

Kelly PA, Gruber SA, Behbod F, Kahan BD. Sirolimus, a new, potent immunosuppressive agent. Pharmacotherapy. 1997;17(6):1148-1156.

Ghadirian P, Jain M, Ducic S, Shatenstein B, Morisset R. Nutritional factors in the aetiology of multiple sclerosis: a case-control study in Montreal, Canada. Int J Epidemiol. 1998;27(5):845-852.

Wang X, Wang W, Xu J, Le Q. Effect of rapamycin and interleukin-2 on regulatory CD4+CD25+Foxp3+ T cells in mice after allogenic corneal transplantation. Transplant Proc. 2013;45(2):528-537.

Rezapour-Firouzi S, Arefhosseini SR, Mehdi F, Mehrangiz EM, Baradaran B, Sadeghihokmabad E, et al. Immunomodulatory and therapeutic effects of Hot-nature diet and co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients. Complement Ther Med. 2013;21(5):473-480.

Rezapour-Firouzi S, Arefhosseini SR, Farhoudi M, Ebrahimi-Mamaghani M, Rashidi MR, Torbati MA, et al. Association of expanded disability status scale and cytokines after intervention with co-supplemented hemp seed, evening primrose oils and hot-natured diet in multiple sclerosis patients♦. Bioimpacts. 2013;3(1):43-47.

Besler HT, Comoglu S, Okcu Z. Serum levels of antioxidant vitamins and lipid peroxidation in multiple sclerosis. Nutr Neurosci. 2002;5(3):215-220.

Rezapour-Firouzi S. Herbal Oil Supplement With Hot-Nature Diet for Multiple Sclerosis. In: Watson RR., Killgore WDS., editors. Nutrition and Lifestyle in Neurological Autoimmune Diseases. USA: Academic Press; 2017. pp. 229-245.

Rezapour-Firouzi S, Arefhosseini SR, Ebrahimi-Mamaghani M, Farhoudi M, Baradaran B, Torbati MA, et al. Erythrocyte membrane fatty acids in multiple sclerosis patients and hot-nature dietary intervention with co-supplemented hemp-seed and evening-primrose oils. Afr J Tradit Complement Altern Med. 2013;10(6):519-527.

Mohammadzadeh A, Pourfathollah AA, Shahrokhi S, Fallah A, Tahoori MT, Amari A, et al. Evaluation of AD-MSC (adipose-derived mesenchymal stem cells) as a vehicle for IFN-beta delivery in experimental autoimmune encephalomyelitis. Clin Immunol. 2016;169:98-106.

Benson JM, Campbell KA, Guan Z, Gienapp IE, Stuckman SS, Forsthuber T, et al. T-cell activation and receptor downmodulation precede deletion induced by mucosally administered antigen. J Clin Invest. 2000;106(8):1031-1038.

Mangalam AK, Luo N, Luckey D, Papke L, Hubbard A, Wussow A, et al. Absence of IFN-gamma increases brain pathology in experimental autoimmune encephalomyelitis-susceptible DRB1*0301.DQ8 HLA transgenic mice through secretion of proinflammatory cytokine IL-17 and induction of pathogenic monocytes/microglia into the central nervous system. J Immunol. 2014;193(10):4859-4870.

Machado AM, de Souza WM, de Padua M, da Machado ARSR, Figueiredo LT. Development of a one-step SYBR Green I real-time RT-PCR assay for the detection and quantitation of Araraquara and Rio Mamore hantavirus. Viruses. 2013;5(9):2272-2281.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-408.

van Meeteren ME, Teunissen CE, Dijkstra CD, van Tol EA. Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur J Clin Nutr. 2005;59(12):1347-1361.

Simopoulos AP, Leaf A, Salem NJr. Workshop statement on the essentiality of and recommended dietary intakes for Omega-6 and Omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2000;63(3):119-121.

Matthaus B, Brühl L. Virgin hemp seed oil: An interesting niche product. Eur J Lipid Sci Technol. 2008;110(7):655-661.

Okuyama H, Kobayashi T, Watanabe S. Dietary fatty acids the N-6/N-3 balance and chronic elderly diseases. Excess linoleic acid and relative N-3 deficiency syndrome seen in Japan. Prog Lipid Res. 1996;35(4):409-457.

Calder PC, Zurier RB. Polyunsaturated fatty acids and rheumatoid arthritis. Curr Opin Clin Nutr Metab Care. 2001;4(2):115-121.

Oomah BD, Busson M, Godfrey DV, Drover JCG. Characteristic of hemp (Cannabis sativa L.) seed oil. Food Chemistry. 2002;76(1):33-43.

Horrobin DF. Multiple sclerosis: the rational basis for treatment with colchicine and evening primrose oil. Med Hypotheses. 1979;5(3):365-378.

Altomare DA, Khaled AR. Homeostasis and the importance for a balance between AKT/mTOR activity and intracellular signaling. Curr Med Chem. 2012;19(22):3748-3762.

Heras-Sandoval D, Perez-Rojas JM, Hernandez-Damian J, Pedraza-Chaverri J. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal. 2014;26(12):2694-2701.

Wahl SE, McLane LE, Bercury KK, Macklin WB, Wood TL. Mammalian target of rapamycin promotes oligodendrocyte differentiation, initiation and extent of CNS myelination. J Neurosci. 2014;34(13):4453-4465.

Ferber IA, Brocke S, Taylor-Edwards C, Ridgway W, Dinisco C, Steinman L, et al. Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunol. 1996;156(1):5-7.

Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, et al. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991;146(10):3444-3451.

Chu CQ, Wittmer S, Dalton DK. Failure to suppress the expansion of the activated CD4 T cell population in interferon gamma-deficient mice leads to exacerbation of experimental autoimmune encephalomyelitis. J Exp Med. 2000;192(1):123-128.

Lee K, Gudapati P, Dragovic S, Spencer C, Joyce S, Killeen N, et al. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity. 2010;32(6):743-753.

Pavlakis M, Goldfarb-Rumyantzev AS. Diabetes after transplantation and sirolimus: what's the connection? J Am Soc Nephrol. 2008;19(7):1255-1256.

Mauvoisin D, Rocque G, Arfa O, Radenne A, Boissier P, Mounier C. Role of the PI3-kinase/mTor pathway in the regulation of the stearoyl CoA desaturase (SCD1) gene expression by insulin in liver. J Cell Commun Signal. 2007;1:113-125.

Peng T, Golub TR, Sabatini DM. The immunosuppressant rapamycin mimics a starvation-like signal distinct from amino acid and glucose deprivation. Mol Cell Biol. 2002;22(15):5575-5584.

Soliman GA. The mammalian target of rapamycin signaling network and gene regulation. Curr Opin Lipidol. 2005;16(3):317-323.

Sachs HH, Bercury KK, Popescu DC, Narayanan SP, Macklin WB. A new model of cuprizone-mediated demyelination/remyelination. ASN Neuro. 2014;6(5). pii:1759091414551955.


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.