The Effects of Evening Primrose/Hemp Seed Oil Compared to Rapamycin on the Gene Expression of Immunological Parameters in Experimental Autoimmune Encephalomyelitis Splenocytes

  • Soheila Rezapour-Firouzi Mail Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
  • Mahshid Mohammadian Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  • Maryam Sadeghzadeh Department ofDepartment of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  • Sahar Mehranfar Department of Immunology and Genetics, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  • Ebrahim Mazloomi Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
Keywords:
Immunologic, Inflammation, Mammalian target of rapamycin, Polyunsaturated fatty acid, Rapamycin

Abstract

Mouse model of multiple sclerosis (MS) is used for the inflammatory demyelinating disease. Rapamycin (RAPA) may contribute to the reduction of inflammatory responses to experimental autoimmune encephalomyelitis (EAE). Due to its adverse side effects, identifying new therapeutic agents is important. We investigated the transcriptional effects of evening primrose/hemp seed oil (EP/HS oil) compared to RAPA on the expression of immunological factors genes in spleen cells of EAE mouse models. We firstly induced EAE mice by injection of myelin oligodendrocyte glycoprotein (MOG). Then, the EAE mice treated and untreated with EP/HS oil were evaluated and compared with naïve mice. The spinal cords were examined histologically. The immunological factors including genes expression of the regulatory-associated protein of mammalian target of rapamycin (RAPTOR), regulatory-associated companion of mammalian target of rapamycin (RICTOR), interferon (IFN)-γ, interleukin (IL)-10, signal transducer and activator of transcription factors (STAT3), forkhead box P3 (FOXP3), and IL-17 of splenocytes were evaluated by real time-polymerase chain reaction (RT-PCR). The data showed that EP/HS oil was able to reduce the severity of EAE and inhibited the development of the disease. EP/HS oil treatment significantly inhibited the expression of RAPTOR, IFN-γ, IL-17, and STAT3 genes and promoted the expression of RICTOR, IL-10, and FOXP3 genes. In conclusion, the EP/HS oil is likely to be involved in transcription of factors in favor of EAE improvement as well as participating in remyelination in the EAE spinal cord and that it suggests to be effective in therapeutic approaches for MS.

References

1. van Meeteren ME, Teunissen CE, Dijkstra CD, et al. Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur J ClinNutr 2005;59(12):1347-1361.
2. Korn T, Reddy J, Gao W, Bettelli E, Awasthi A, Petersen TR, et al. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med 2007;13(4):423-31.
3. Takei N, Nawa H. mTOR signaling and its roles in normal and abnormal brain development. Front Mol Neurosci 2014;7:28.
4. Fernandez D, Perl A. mTOR signaling: a central pathway to pathogenesis in systemic lupus erythematosus? Discov Med 2010;9(46):173-8.
5. Zhao YG, Wang Y, Guo Z, Gu AD, Dan HC, Baldwin AS, et al. Dihydroartemisinin ameliorates inflammatory disease by its reciprocal effects on Th and regulatory T cell function via modulating the mammalian target of rapamycin pathway. J Immunol 2012;189(9):4417-25.
6. Delgoffe GM, Pollizzi KN, Waickman AT, Heikamp E, Meyers DJ, Horton MR, et al. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat Immunol 2011;12(4):295-303.
7. Korn T, Anderson AC, Bettelli E, Oukka M. The dynamics of effector T cells and Foxp3+ regulatory T cells in the promotion and regulation of autoimmune encephalomyelitis. J Neuroimmunol 2007;191(1-2):51-60.
8. Sarbassov DD, Ali SM, Sengupta S, et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006;22(2):159-68.
9. Laplante M, Sabatini DM. An emerging role of mTOR in lipid biosynthesis. Curr Biol 2009;19(22):R1046-52.
10. Yuan LF, Li GD, Ren XJ, Nian H, Li XR, Zhang XM. Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting Th1/Th2/Th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells. Int J Ophthalmol 2015;8(4):659-64.
11. Krogulska A, Borowiec M, Polakowska E, et al. FOXP3, IL-10, and TGF-beta genes expression in children with IgE-dependent food allergy. J Clin Immunol 2011;31(2):205-15.
12. Jump DB, Tripathy S, Depner CM. Fatty acid-regulated transcription factors in the liver. Annu Rev Nutr 2013;33:249-69.
13. Pollizzi KN, Powell JD. Regulation of T cells by mTOR: the known knowns and the known unknowns. Trends Immunol 2015;36(1):13-20.
14. 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. Elsevier: Academic Press 2017:229-45.
15. Simopoulos AP, Leaf A, Salem N, Jr. 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):119-21.
16. Matthaus B, Brühl L. Virgin hemp seed oil: An interesting niche product. Eur J Lipid Sci Technol 2008;110(7):655-61.
17. Rezapour-Firouzi S, Arefhosseini SR, Ebrahimi-Mamaghani M, Farhoudi M, Baradaran B, Ali TM, 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):519-27.
18. Rahn EJ, Iannitti T, Donahue RR, Taylor BK. Sex differences in a mouse model of multiple sclerosis: neuropathic pain behavior in females but not males and protection from neurological deficits during proestrus Biol Sex Differ 2014;5(1):4.
19. Okuda Y, Okuda M, Bernard CC. Gender does not influence the susceptibility of C57BL/6 mice to develop chronic experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein. Immunol Lett 2002;81(1):25-9.
20. 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):1031-8.
21. Rezapour-Firouzi S, Shahabi S, Mohammadzadeh A, Tehrani AA, Kheradmand F, Mazloomi E. The potential effects of hemp seed/evening primrose oils on the mammalian target of rapamycin complex 1 and interferon-gamma genes expression in experimental autoimmune encephalomyelitis. Res Pharm Sci 2018;13(6):523-32.
22. Rezapour-Firouzi S, Arefhosseini SR, Mehdi F, 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):473-80.
23. Lisi L, Aceto P, Navarra P, Dello Russo C. mTOR kinase: a possible pharmacological target in the management of chronic pain. Biomed Res Int 2015;2015:394257.
24. 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):4859-70.
25. 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):402-8.
26. 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.
27. Caron A, Richard D, Laplante M. The Roles of mTOR Complexes in Lipid Metabolism. Annu Rev Nutr 2015;35:321-48.
28. Yang K, Shrestha S, Zeng H, Karmaus PW, Neale G, Vogel P, et al. T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming. Immunity 2013;39(6):1043-56.
29. Chakrabarti P, Kandror KV. The role of mTOR in lipid homeostasis and diabetes progression. Curr Opin Endocrinol Diabetes Obes 2015;22(5):340-6.30. Pavlakis M, G
























oldfarb-Rumyantzev AS. Diabetes after transplantation and sirolimus: what's the connection? J Am Soc Nephrol 2008;19(7):1255-6.
31. Stylianou K, Petrakis I, Mavroeidi V, Stratakis S, Vardaki E, Perakis K, et al. The PI3K/Akt/mTOR pathway is activated in murine lupus nephritis and downregulated by rapamycin. Nephrol Dial Transplant 2011;26(2):498-508.
32. Narayanan SP, Flores AI, Wang F, Macklin WB. Akt signals through the mammalian target of rapamycin pathway to regulate CNS myelination. J Neurosci 2009;29(21):6860-70.
Published
2020-04-16
How to Cite
1.
Rezapour-Firouzi S, Mohammadian M, Sadeghzadeh M, Mehranfar S, Mazloomi E. The Effects of Evening Primrose/Hemp Seed Oil Compared to Rapamycin on the Gene Expression of Immunological Parameters in Experimental Autoimmune Encephalomyelitis Splenocytes. Iran J Allergy Asthma Immunol. 19(2):183-192.
Section
Original Article(s)