AIMS Medical Science, 2019, 6(2): 140-147. doi: 10.3934/medsci.2019.2.140 Research article Special Issues

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Down-regulation of IRF3 expression in Relapse-Remitting MS patients

Sobhan Helbi, Zahra Engardeh, Sahar Nickbin Poshtamsary, Zaynab Aminzadeh, Nahid Jivad

1 School of Medicine, Dezful University of Medical Sciences, Dezful, Iran
2 Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
3 School of Nursing and Midwifery, Guilan University of Medical Sciences, Rasht, Iran
4 Department of Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
5 Department of Neurology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran

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Special Issues: Innovations in Immunology

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Background: Relapsing-Remitting (RRMS) is the most common Multiple Sclerosis disease course. Interferon regulatory factor 3 (IRF3) as major regulators of immune system genes plays a critical role in the activation of type I interferons promoters, in particular IFNβ promoter. Hence we aimed to evaluate the expression rate of IRF3 in RRMS patients under different type of IFNβ treatment. Material and methods: In the present study total of 100 subjects participated. Blood samples of 25 patients with RRMS newly diagnosed who have not been treated with interferon components, 25 patients with RRMS treated with Interferon beta-1α (B1a), 25 patients with RRMS treated with Interferon beta-1β (B1b) and 25 control samples were collected. The samples were transferred at standard conditions to the Cellular and Molecular Research Center of Shahrekord University of Medical Sciences, RNA was extracted and converted to cDNA. To evaluate the expression of IRF3 the Real-Time PCR method using SYBR Green dye was done. The level of gene expression was measured by a comparative threshold cycle formula. The obtained data were analyzed using SPSS v15 software. Results: In the study we compared the IRF3 mRNA expression of all subjects in association with gender, which no significant difference was seen (P > 0.05). Also assessment of the gene mRNA level in study groups revealed that the B1b, B1a and new case group had the lowest expression respectively. Moreover, comparison of the mRNA level between new case and B1b groups showed remarkable difference (P < 0.05). According to age and sex factors, no remarkable differences between study groups were seen (P > 0.05). Conclusion: Perhaps the IFNβ recombinants decreases the IRF3 expression as a negative feedback mechanism. Overall the data reported here, supports the previous studies in important role of IRF3 in autoimmune inflammatory disease of CNS and Multiple Sclerosis.

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1. Pugliatti M, Rosati G, Carton H, et al. (2006) Epidemiology of multiple sclerosis in Europe. Eur J Neurol 13: 700–722.

2. Eskandarieh S, Heydarpour P, Elhami SR, et al. (2017) Prevalence and Incidence of Multiple Sclerosis in Tehran, Iran. Iran J Public Health 46: 699–704.

3. Fletcher JM, Lalor SJ, Sweeney CM, et al. (2010) T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol 162: 1–11.

4. McCandless EE, Piccio L, Woerner BM, et al. (2008) Pathological expression of CXCL12 at the blood-brain barrier correlates with severity of multiple sclerosis. Am J Pathol 172: 799–808.

5. Goldenberg MM (2012) Multiple sclerosis review. P T 37: 175–184.

6. Tarassishin L, Bauman A, Suh HS, et al. (2013) Anti-viral and anti-inflammatory mechanisms of the innate immune transcription factor interferon regulatory factor 3: relevance to human CNS diseases. J Neuroimmune Pharmacol 8: 132–144.

7. Oshiumi H, Matsumoto M, Funami K, et al. (2003) TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat Immunol 4: 161–167.

8. Matta B, Song S, Li D, et al. (2017) Interferon regulatory factor signaling in autoimmune disease. Cytokine 98: 15–26.

9. Madsen C (2017) The innovative development in interferon beta treatments of relapsing-remitting multiple sclerosis. Brain Behav 7: e00696.

10. Reder AT, Feng X (2014) How type I interferons work in multiple sclerosis and other diseases: some unexpected mechanisms. J Interferon Cytokine Res 34: 589–599.

11. Yanai H, Chiba S, Hangai S, et al. (2018) Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice. Proc Natl Acad Sci U S A 115: 5253–5258.

12. Touil T, Fitzgerald D, Zhang GX, et al. (2006) Cutting Edge: TLR3 stimulation suppresses experimental autoimmune encephalomyelitis by inducing endogenous IFN-beta. J Immunol 177: 7505–7509.

13. Thompson AJ, Banwell BL, Barkhof F, et al. (2018) Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 17: 162–173.

14. Mao P, Reddy PH (2010) Is multiple sclerosis a mitochondrial disease? Biochim biophys Acta 1802: 66–79.

15. Pajouh SD, Moradi N, Shaterzadeh Yazdi MJ, et al. (2017) Diagnostic evaluation of dysphagia in multiple sclerosis patients using a Persian version of DYMUS questionnaire. Mult Scler Related Disord 17: 240–243.

16. Poorjavad M, Derakhshandeh F, Etemadifar M, et al. (2010) Associated Factors with Swallowing Disorders in Patients with Multiple Sclerosis. J Isfahan Med Sch 28: 44–51.

17. Schultz KLW, Troisi EM, Baxter VK, et al. (2018) Interferon regulatory factors 3 and 7 have distinct roles in the pathogenesis of alphavirus encephalomyelitis. J Gen Virol 100: 46–62.

18. Tarassishin L, Loudig O, Bauman A, et al. (2011) Interferon regulatory factor 3 inhibits astrocyte inflammatory gene expression through suppression of the proinflammatory miR-155 and miR-155*. Glia 59: 1911–1922.

19. Feng X, Petraglia AL, Chen M, et al. (2002) Low expression of interferon-stimulated genes in active multiple sclerosis is linked to subnormal phosphorylation of STAT1. J Neuroimmunol 129: 205–215.

20. Panitch H, Miller A, Paty D, et al. (2004) Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology 63: 1788–1795.

21. Guarda G, Braun M, Staehli F, et al. (2011) Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity 34: 213–223.

22. Hu X, Ho HH, Lou O, et al. (2005) Homeostatic role of interferons conferred by inhibition of IL-1-mediated inflammation and tissue destruction. J Immunol 175: 131–138.

23. Downer EJ, Clifford E, Gran B, et al. (2011) Identification of the synthetic cannabinoid R(+)WIN55,212-2 as a novel regulator of IFN regulatory factor 3 activation and IFN-beta expression: relevance to therapeutic effects in models of multiple sclerosis. J Biol Chem 286: 10316–10328.

24. Cerqueira JJ, Compston DAS, Geraldes R, et al. (2018) Time matters in multiple sclerosis: can early treatment and long-term follow-up ensure everyone benefits from the latest advances in multiple sclerosis? J Neurol Neurosurg Psychiatry 89: 844–850.

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