Different Expressions of Specific Transcription Factors of Th1 (T-bet) and Th2 cells (GATA-3) by Peripheral Blood Mononuclear Cells From Patients With Multiple Sclerosis

Etesam, Zahra; Nemati, Maryam; Ebrahimizadeh, Mohammad-Amin; Ebrahimi, Hossain-Ali; Hajghani, Hossain; Khalili, Tahereh; Jafarzadeh, Abdollah

doi:10.32598/bcn.9.6.458

Volume 9, Issue 6 (November & December 2018) BCN 2018, 9(6): 458-469 | Back to browse issues page

‎ 10.32598/bcn.9.6.458

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Etesam Z, Nemati M, Ebrahimizadeh M, Ebrahimi H, Hajghani H, Khalili T et al . Different Expressions of Specific Transcription Factors of Th1 (T-bet) and Th2 cells (GATA-3) by Peripheral Blood Mononuclear Cells From Patients With Multiple Sclerosis. BCN 2018; 9 (6) :458-469
URL: http://bcn.iums.ac.ir/article-1-744-en.html

Different Expressions of Specific Transcription Factors of Th1 (T-bet) and Th2 cells (GATA-3) by Peripheral Blood Mononuclear Cells From Patients With Multiple Sclerosis

Zahra Etesam¹

, Maryam Nemati²

, Mohammad-Amin Ebrahimizadeh²

, Hossain-Ali Ebrahimi¹

, Hossain Hajghani²

, Tahereh Khalili³

, Abdollah Jafarzadeh ^*

⁴

1- Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran.
2- Department of Immunology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
3- Department of Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
4- Department of Immunology, School of Medical, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

Abstract:

Introduction: Multiple Sclerosis (MS) is an inflammatory disorder caused by self-reactive Th1 lymphocytes, while Th2 cells may confer protection. The Th1 and Th2 cell differentiation are regulated by specific transcription factors, especially T-bet and GATA-3, respectively. This investigation aimed to measure the T-bet and GATA-3 expression by Peripheral Blood Mononuclear Cells (PBMCs) obtained from MS patients after specific and non-specific in vitro stimulation.
Methods: The PBMCs were separated from 22 patients with MS and 20 healthy individuals. They were cultured at 37°C for 24 h in the absence of a stimulator or in the presence of Myelin oligodendrocyte Glycoprotein (MOG) or Phytohemagglutinin (PHA) at a concentration of 10 μg/mL. Then the T-bet and GATA-3 expression was measured by real time-PCR.
Results: The T-bet expression was enhanced, while the GATA-3 expression diminished. Therefore the expression of T-bet/GATA-3 ratio diminished in not-stimulated, MOG-stimulated and PHA-stimulated PBMCs from MS patients compared with equal cultures from the healthy individuals (P<0.01, P<0.01 and P<0.01, for T-bet; P<0.03, P<0.01 and P<0.02, for GATA-3; P<0.01, P<0.001 and P<0.01 for T-bet/GATA-3 ratio, respectively). The not-stimulated, MOG-stimulated, and PHA-stimulated PBMCs from men with MS expressed higher amounts of GATA-3 than equal cells from MS women (P<0.05, P<0.05 and P<0.01, respectively).
Conclusion: These results probably indicate an imbalance in Th1/Th2 cells in the level of transcription factors with a tendency toward Th1 cells in MS. The clinical utilization of the transcription factors as novel biomarkers of MS should be evaluated in further studies.

Keywords: Multiple Sclerosis, Th1, Th2, T-bet, GATA-3

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Type of Study: Original | Subject: Cellular and molecular Neuroscience
Received: 2016/03/10 | Accepted: 2018/04/20 | Published: 2018/11/1

References

1. Ebrahimi, H. A., & Sedighi, B. (2013). Prevalence of multiple sclerosis and environmental factors in Kerman province, Iran. Neurology Asia, 18(4), 385–9.

2. Edstrom, M., Mellergard, J., Mjosberg, J., Jenmalm, M., Vrethem, M., Press, R., et al. (2011). Transcriptional characteristics of CD4+ T cells in multiple sclerosis: Relative lack of suppressive populations in blood. Multiple Sclerosis, 17(1), 57-66. [DOI:10.1177/1352458510381256] [DOI:10.1177/1352458510381256]

3. Etesam, Z., Nemati, M., Ebrahimizadeh, M. A., Ebrahimi, H. A., Hajghani, H., Khalili, T., et al. (2016). Altered expression of specific transcription factors of 17th (RORgammat, RORalpha) and treg lymphocytes (FOXP3) by peripheral blood mononuclear cells from patients with multiple sclerosis. Journal of Molecular Neuroscience, 60(1), 94-101. [DOI:10.1007/s12031-016-0789-5] [PMID] [DOI:10.1007/s12031-016-0789-5]

4. Evans, C. M., & Jenner, R. G. (2013). Transcription factor interplay in T helper cell differentiation. Briefings in Functional Genomics, 12(6), 499-511. [DOI:10.1093/bfgp/elt025] [PMCID] [DOI:10.1093/bfgp/elt025]

5. Fernando, V., Omura, S., Sato, F., Kawai, E., Martinez, N. E., Elliott, S. F., et al. (2014) Regulation of an autoimmune model for multiple sclerosis in Th2-biased GATA-3 transgenic mice. International Journal of Molecular Sciences, 15(2), 1700-18. [DOI:10.3390/ijms15021700] [PMCID] [DOI:10.3390/ijms15021700]

6. Hirahara, K., & Nakayama, T. (2016). CD4+ T-cell subsets in inflammatory diseases: Beyond the Th1/Th2 paradigm. International Immunology, 28(4), 163-71. [DOI:10.1093/intimm/dxw006] [DOI:10.1093/intimm/dxw006]

7. Jafarzadeh, A., Ahangar Parvin, R., Nemati, M., Taghipour, Z., Shamsizadeh, A., & Ayoobi, F. (2017). Ginger extract modulates the expression of IL-12 and TGF-β in the central nervous system and serum of mice with experimental autoimmune encephalomyelitis. Avicenna Journal of Phytomedicine, 7(1), 54-65. [PMID] [PMID] [PMCID]

8. Jafarzadeh, A., Azizi, S. V., Nemati, M., Khoramdel Azad, H., Shamsizadeh, A., Ayoobi, F., et al. (2015a). Ginger extract reduces the expression of IL-17 and IL-23 in the sera and central nervous system of EAE mice. Iranian Journal of Immunology, 12(4), 288-301. [DOI:IJIv12i4A6] [PMID] [PMID]

9. Jafarzadeh, A., Bagherzadeh, S., Ebrahimi, H. A., Hajghani, H., Bazrafshani, M.R., Khosravimashizi, A., et al. (2014a). Higher circulating levels of chemokine CCL20 in patients with multiple sclerosis: Evaluation of the influences of chemokine gene polymorphism, gender, treatment and disease pattern. Journal of Molecular Neuroscience, 53(3), 500-5. [DOI:10.1007/s12031-013-0214-2 [DOI:10.1007/s12031-013-0214-2]

10. Jafarzadeh, A., Ebrahimi, H. A., Bagherzadeh, S., Zarkesh, F., Iranmanesh, F., Najafzadeh, A., et al. (2014b). Lower serum levels of Th2-related chemokine CCL22 in women patients with multiple sclerosis: A comparison between patients and healthy women. Inflammation, 37(2), 604-10. [DOI:10.1007/s10753-013-9775-z] [PMID]

11. Jafarzadeh, A., Jamali, M., Mahdavi, R., Ebrahimi, H. A., Hajghani, H., Khosravimashizi, A., et al. (2015b). Circulating levels of interleukin-35 in patients with multiple sclerosis: Evaluation of the influences of FOXP3 gene polymorphism and treatment program. Journal of Molecular Neuroscience, 55(4), 891-7. [DOI:10.1007/s12031-014-0443-z] [PMID] [DOI:10.1007/s12031-014-0443-z]

12. Jafarzadeh, A., Mahdavi, R., Jamali, M., Hajghani, H., Nemati, M., & Ebrahimi, H. A. (2016). Increased concentrations of interleukin-33 in the serum and cerebrospinal fluid of patients with multiple sclerosis. Oman Medical Journal, 31(1), 40-5. [DOI:10.5001/omj.2016.08] [PMCID] [PMID] [DOI:10.5001/omj.2016.08]

13. Jafarzadeh, A., Mohammadi Kordkhayli, M., Ahangar Parvin, R., Azizi, V., Khoramdel Azad, H., et al. (2014c). Ginger extracts influence the expression of IL-27 and IL-33 in the central nervous system in experimental autoimmune encephalomyelitis and ameliorates the clinical symptoms of disease. Journal of Neuroimmunology, 276(1-2), 80-8. [DOI:10.1016/j.jneuroim.2014.08.614] [DOI:10.1016/j.jneuroim.2014.08.614]

14. Kallaur, A. P., Oliveira, S. R., Colado Simao, A. N., Delicato de Almeida, E. R., Kaminami Morimoto, H., Lopes, J., et al. (2013). Cytokine profile in relapsingremitting multiple sclerosis patients and the association between progression and activity of the disease. Molecular Medicine Reports, 7(3), 1010-20. [DOI:10.3892/mmr.2013.1256] [DOI:10.3892/mmr.2013.1256]

15. Kostic, M., Stojanovic, I., Marjanovic, G., Zivkovic, N., & Cvetanovic, A. (2015). Deleterious versus protective autoimmunity in multiple sclerosis. Cellular Immunology, 296, 122-32. [DOI:10.1016/j.cellimm.2015.04.006] [DOI:10.1016/j.cellimm.2015.04.006]

16. La Flamme, A. C., Harvie, M., McNeill, A., Goldsack, L., Tierney, J. B., & Bäckström, B. T. (2006). Fcγ receptor-ligating complexes improve the course of experimental autoimmune encephalomyelitis by enhancing basal Th2 responses. Immunology and Cell Biology, 84(6), 522-9. [DOI:10.1111/j.1440-1711.2006.01464.x] [DOI:10.1111/j.1440-1711.2006.01464.x]

17. Lin, Z. W., Wu, L. X., Xie, Y., Ou, X., Tian, P. K., Liu, X. P., et al. (2015). The expression levels of transcription factors T-bet, GATA-3, RORgammat and FOXP3 in Peripheral Blood Lymphocyte (PBL) of patients with liver cancer and their significance. International Journal of Medical Sciences, 12(1), 7-16. [DOI:10.7150/ijms.8352] [PMCID] [DOI:10.7150/ijms.8352]

18. Mahad, D. H., Trapp, B. D., & Lassmann, H. (2015) Pathological mechanisms in progressive multiple sclerosis. The Lancet Neurology, 14(2), 183-93. [DOI:10.1016/S1474-4422(14)70256-X]

19. Martinez, N.E., Sato, F., Omura, S., Kawai, E., Takahashi, S., Yoh, K., et al. (2014). RORgammat, but not T-bet, overexpression exacerbates an autoimmune model for multiple sclerosis. Journal of Neuroimmunology, 276(0), 142-9. [DOI:10.1016/j.jneuroim.2014.09.006] [DOI:10.1016/j.jneuroim.2014.09.006]

20. McDonald, W. I., Compston, A., Edan, G., Goodkin, D., Hartung, H. P., Lublin, F. D., et al. (2001). Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis. Annals of Neurology, 50(1), 121-7. [DOI:10.1002/ana.20849] [PMID] [DOI:10.1002/ana.20849]

21. Na, H., Cho, M. & Chung, Y. (2016). Regulation of Th2 cell immunity by dendritic cells. Immune Network, 16, 1-12. [Doi:10.4110/in.2016.16.1.1] [DOI:10.4110/in.2016.16.1.1]

22. Ngo, S. T., Steyn, F. J., & McCombe, P. A. (2014). Gender differences in autoimmune disease. Frontiers in Neuroendocrinology, 35(3), 347-69. [DOI:10.1016/j.yfrne.2014.04.004] [DOI:10.1016/j.yfrne.2014.04.004]

23. Oreja Guevara, C., Ramos-Cejudo, J., Aroeira, L. S., Chamorro, B., & Diez Tejedor, E. (2012). TH1/TH2 cytokine profile in relapsing-remitting multiple sclerosis patients treated with Glatiramer acetate or Natalizumab. BMC Neurology,12, 95. [DOI:10.1186/1471-2377-12-95] [PMCID] [DOI:10.1186/1471-2377-12-95]

24. Pedotti, R., Farinotti, M., Falcone, C., Borgonovo, L., Confalonieri, P., Campanella, A., et al. (2009). Allergy and multiple sclerosis: A population-based case-control study. Multiple Sclerosis, 15, 899-906. [DOI:10.1177/1352458509106211] [PMID] [DOI:10.1177/1352458509106211]

25. Raphael, I., Nalawade, S., Eagar, T. N., & Forsthuber, T. G. (2015). T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine, 74, 5-17. [DOI:10.1016/j.cyto.2014.09.011] [PMCID] [DOI:10.1016/j.cyto.2014.09.011]

26. Uysal, S., Meric Yilmaz, F., Bogdaycioglu, N., Mungan Ozturk, S., & Ak, F. (2014) Increased serum levels of some inflammatory markers in patients with multiple sclerosis. Minerva Medica, 105, 229-35. [DOI:10.4172/2329-6895.S1.003] [DOI:10.4172/2329-6895.S1.003]

27. Zhang, Y., Zhang, Y., Gu, W., He, L., & Sun, B. (2014a). Th1/Th2 cell's function in immune system. Advances in Experimental Medicine and Biology, 841, 45-65. [DOI:10.1007/978-94-017-9487-9_3] [DOI:10.1007/978-94-017-9487-9_3]

28. Zhang, Y., Zhang, Y., Gu, W. & Sun, B. (2014b). TH1/TH2 cell differentiation and molecular signals. Advances in Experimental Medicine and Biology, 841, 15-44. [DOI:10.1007/978-94-017-9487-9_2] [DOI:10.1007/978-94-017-9487-9_2]

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