Evaluation of mRNA Expression Levels of IL-10, IL-12, TGF-β, FOXP3, IFN in Multiple Sclerosis Patients

Abstract

Background: Although great advances have been made in the treatment of Multiple Sclerosis (MS), a neurodegenerative disease due to autoimmune inflammation, the etiopathogenesis of the disease has not yet been fully understood. Therefore, current treatment strategies may be insufficient. This study, it was aimed to quantitatively measure the expression levels of some cytokines determined in patients receiving MS treatment. Methods: This study was carried out on patients diagnosed with MS and healthy volunteers followed in Atatürk University Health Research and Application Center Neurology Department, Erzurum, Turkey. mRNA expression changes of IL-10, IL-12, TGF-β, FOXP3, and IFN genes in blood samples taken from both groups were determined by quantitative Real-Time PCR. Results: It was determined that there was no statistically significant difference between the patient and control group in the mRNA expression levels of the IL-10 and FOXP3 genes. A statistically significant difference was observed between the patient and control group in TGF-β, IL-12, and IFN mRNA levels. Conclusion: In this study, it was determined that important information about the course of the disease can be obtained by evaluating the expression levels of regulator genes in MS, together

Keywords

• Biomarker
• Cytokines
• Gene expression
• Multiple sclerosis

References

1. Ascherio A, Munger KL, Lunemann JD. The initiation and prevention of multiple sclerosis. Nat Rev Neurol 2012; 8(11): 602-12.
2. Dobson R, Giovannoni G. Multiple sclerosis - a review. Eur J Neurol 2019; 26(1): 27-40.
3. Ascherio A. Environmental factors in multiple sclerosis. Expert Rev Neurother 2013; 13(12 Suppl): 3-9 . Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S, et al. Multiple sclerosis. Nat Rev Dis Primers 2018; 4(1): 43.
4. Baranzini SE, Oksenberg JR. The Genetics of Multiple Sclerosis: From 0 to 200 in 50 Years. Trends Genet 2017; 33(12): 960-70 . Hashemi R, Morshedi M, Asghari Jafarabadi M, Altafi D, Saeed Hosseini-Asl S, Rafie-Arefhosseini S. Anti-inflammatory effects of dietary vitamin D3 in patients with multiple sclerosis. Neurol Genet 2018; 4(6): e278.
5. Hashemi R, Hosseini-Asl SS, Arefhosseini SR, Morshedi M. The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives. PLoS One 2020; 15(4): e0231145.
6. Arellano G, Acuna E, Reyes LI, Ottum PA, De Sarno P, Villarroel L, et al. Th1 and Th17 Cells and Associated Cytokines Discriminate among Clinically Isolated Syndrome and Multiple Sclerosis Phenotypes. Front Immunol 2017; 8: 753.
7. Palle P, Monaghan KL, Milne SM, Wan ECK. Cytokine Signaling in Multiple Sclerosis and Its Therapeutic Applications. Med Sci (Basel) 2017; 5(4).
8. Mirshafiey A, Mohsenzadegan M. TGF-beta as a promising option in the treatment of multiple sclerosis. Neuropharmacology 2009; 56(6-7): 929-36.

9. Williams SK, Maier O, Fischer R, Fairless R, Hochmeister S, Stojic A, et al. Antibody-mediated inhibition of TNFR1 attenuates disease in a mouse model of multiple sclerosis. PLoS One 2014; 9(2): e90117.
10. Hendrickx DAE, van Scheppingen J, van der Poel M, Bossers K, Schuurman KG, van Eden CG, et al. Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions. Front Immunol 2017; 8: 1810.
11. Kobelt G, Thompson A, Berg J, Gannedahl M, Eriksson J, Group MS, et al. New insights into the burden and costs of multiple sclerosis in Europe. Mult Scler 2017; 23(8): 1123-36.
12. Balkan E, Bilge N. Expression levels of IL-17/IL-23 cytokine-targeting microRNAs 20, 21, 26, 155, and Let-7 in patients with relapsing-remitting multiple sclerosis. Neurol Res 2021; 43(9): 778-83.
13. Browne P, Chandraratna D, Angood C, Tremlett H, Baker C, Taylor BV, et al. Atlas of Multiple Sclerosis 2013: A growing global problem with widespread inequity. Neurology 2014; 83(11): 1022-4.
14. Monforte J, McPhail S. Strategy for gene expression-based biomarker discovery. Biotechniques 2005; Suppl: 25-9.
15. van't Veer LJ, Paik S, Hayes DF. Gene expression profiling of breast cancer: a new tumor marker. J Clin Oncol 2005; 23(8): 1631-5.
16. Wei JS, Greer BT, Westermann F, Steinberg SM, Son CG, Chen QR, et al. Prediction of clinical outcome using gene expression profiling and artificial neural networks for patients with neuroblastoma. Cancer Res 2004; 64(19): 6883-91.
17. Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol 1995; 13: 251-76.
18. Balashov KE, Smith DR, Khoury SJ, Hafler DA, Weiner HL. Increased interleukin 12 production in progressive multiple sclerosis: induction by activated CD4+ T cells via CD40 ligand. Proc Natl Acad Sci U S A 1997; 94(2): 599-603.
19. Kallaur AP, Oliveira SR, Colado Simao AN, Delicato de Almeida ER, Kaminami Morimoto H, Lopes J, et al. Cytokine profile inrelapsingremitting multiple sclerosis patients and the association between progression and activity of the disease. Mol Med Rep 2013; 7(3): 1010-20.
20. Huang WX, Huang P, Hillert J. Increased expression of caspase-1 and interleukin-18 in peripheral blood mononuclear cells in patients with multiple sclerosis. Mult Scler 2004; 10(5): 482-7.
21. Lee PW, Severin ME, Lovett-Racke AE. TGF-beta regulation of encephalitogenic and regulatory T cells in multiple sclerosis. Eur J Immunol 2017; 47(3): 446-53.
22. Kuruvilla AP, Shah R, Hochwald GM, Liggitt HD, Palladino MA, Thorbecke GJ. Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice. Proc Natl Acad Sci U S A 1991; 88(7): 2918-21.
23. Johns LD, Flanders KC, Ranges GE, Sriram S. Successful treatment of experimental allergic encephalomyelitis with transforming growth factor-beta 1. J Immunol 1991; 147(6): 1792-6.
24. Isik N, Yildiz Manukyan N, Aydin Canturk I, Candan F, Unsal Cakmak A, Saru Han Direskeneli G. Genetic Susceptibility to Multiple Sclerosis: The Role of FOXP3 Gene Polymorphism. Noro Psikiyatr Ars 2014; 51(1): 69-73
25. Li Z, Li D, Tsun A, Li B. FOXP3+ regulatory T cells and their functional regulation. Cell Mol Immunol 2015; 12(5): 558-65.
26. Eftekharian MM, Sayad A, Omrani MD, Ghannad MS, Noroozi R, Mazdeh M, et al. Single nucleotide polymorphisms in the FOXP3 gene are associated with increased risk of relapsing-remitting multiple sclerosis. Hum Antibodies 2016; 24(3-4): 85-90.
27. Huan J, Culbertson N, Spencer L, Bartholomew R, Burrows GG, Chou YK, et al. Decreased FOXP3 levels in multiple sclerosis patients. J Neurosci Res 2005; 81(1): 45-52.