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 IJCM  Vol.7 No.9 , September 2016
Investigating the Extent of CCL4 and CCL5 Chemokine as Well as IL17 and IL23 Cytokine Gene Expression in the Patients Afflicted with Multiple Sclerosis
Abstract: MS is a chronic inflammatory disease of central nervous system in which T cells enter central nervous system and create an inflammatory cascade that leads to applying the other blood cells. Pre-inflammatory Cytokines are representative of the process of inflammatory diseases like MS. In addition, the increase of such cytokines has been observed in this kind of anomalies. On the other hand, helping T cells of 17 (TH17) contributes to the secretion of interleukin 17 that is a pre-inflammatory cytokine and an increase in TH17 cells is induced by interleukin 23 (IL23) which in turn causes absorption of neutrophils in the site of inflammation. Chemokine also has a determining function in the immune system including Ccl4 protein sit, the function of which is chemical absorption for calling natural fatal cells and monocytes as well as the other immune system cells; additionally, Ccl5 causes chemical absorption to absorb Eosinophil and Basophil and has an active role in applying Leukocytesin the site of inflammation. As a result, these 4 factors can hurt nervous cell through increasing its expression and calling leukocytes. The expression of these 4 genes, corticosteroid treatment and investigating its impact on changing the expression of such genes are the aims of this study. In this study 50 samples of blood of people suffer from multiple sclerosis (according to the diagnosis of specialist) (new case), 25 samples of blood of people suffer from MS (according to the diagnosis of specialist) using corticosteroid and 50 blood samples of healthy people without any symptoms were compared. To investigate the extent of expression of IL23, IL-17, CCL5 and CCL4 genes, first, the patients’ blood is taken, RNA was extracted and Real Time PCR was carried out. According to the results obtained from Real Time PCR of patients and healthy people it was specified that the amount of expression of chemokine and cytokines is increased in the people suffering from MS and has a direct relationship with MS. In comparing the two groups of patients (new case and people taking medicine) it was revealed that the amount of expression of IL17, IL23, CCL4 and CCL5 genes is decreased in people who take medicine. An increase in the expression of IL17, IL23, CCL4 and CCL5 genes is the symptom of MS disease and contributes to its creation and progression. The difference in the expression of chemokine and cytokine genes can be used as an identifying maker in this disease. On the other hand, corticosteroid medicine can have a determining role in the increase of expression as well as the destructive function of immune system.
Cite this paper: Hajiannasab, R. (2016) Investigating the Extent of CCL4 and CCL5 Chemokine as Well as IL17 and IL23 Cytokine Gene Expression in the Patients Afflicted with Multiple Sclerosis. International Journal of Clinical Medicine, 7, 598-607. doi: 10.4236/ijcm.2016.79066.
References

[1]   Branas, P., Jordan, R., Fry-Smith, A., Burls, A. and Hyde, C. (2000) Treatments for Fatigue in Multiple Sclerosis: A Rapid and Systematic Review. National Coordinating Centre for HTA, London, Great Britain.

[2]   Krupp, L.B. and Rizvi, S.A. (2002) Symptomatic Therapy for Underrecognized Manifestations of Multiple Sclerosis. Neurology, 58, S32-S39.
http://dx.doi.org/10.1212/WNL.58.8_suppl_4.S32

[3]   Sheean, G.L., Murray, N., Rothwell, J.C., Miller, D.H. and Thompson, A.J. (1997) An Electrophysiological Study of the Mechanism of Fatigue in Multiple Sclerosis. Brain, 120, 299-315.
http://dx.doi.org/10.1093/brain/120.2.299

[4]   Rudick, R.A. and Barna, B.P. (1990) Serum Interleukin 2 and Soluble Interleukin 2 Receptor in Patients with Multiple Sclerosis Who Are Experiencing Severe Fatigue. Archives of Neurology, 47, 254-255.
http://dx.doi.org/10.1001/archneur.1990.00530030018008

[5]   Kivisäkk, P., Liu, Z., Trebst, C., Tucky, B., Wu, L., Stine, J., et al. (2003) Flow Cytometric Analysis of Chemokine Receptor Expression on Cerebrospinal Fluid Leukocytes. Methods, 29, 319-325.
http://dx.doi.org/10.1016/S1046-2023(02)00355-9

[6]   Miller, D.H., Khan, O.A., Sheremata, W.A., Blumhardt, L.D., Rice, G.P., Libonati, M.A., et al. (2003) A Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis. New England Journal of Medicine, 348, 15-23.
http://dx.doi.org/10.1056/NEJMoa020696

[7]   Nelson, P.J. and Krensky, A.M. (2001) Chemokines, Chemokine Receptors, and Allograft Rejection. Immunity, 14, 377-386.
http://dx.doi.org/10.1016/S1074-7613(01)00118-2

[8]   Ebers, G.C. and Sadovnick, A.D. (1993) The Geographic Distribution of Multiple Sclerosis: a Review. Neuroepidemiology, 12, 1-5.
http://dx.doi.org/10.1159/000110293

[9]   Goris, A., Epplen, C., Fiten, P., Andersson, M., Murru, R., Sciacca, F.L., et al. (1999) Analysis of an IFN-Gamma Gene (IFNG) Polymorphism in Multiple Sclerosis in Europe: Effect of Population Structure on Association with Disease. Journal of Interferon & Cytokine Research, 19, 1037-1046.
http://dx.doi.org/10.1089/107999099313262

[10]   Ebers, G.C., Bulman, D.E., Sadovnick, A.D., Paty, D.W., Warren, S., Hader, W., et al. (1986) A Population-Based Study of Multiple Sclerosis in Twins. New England Journal of Medicine, 315, 1638-1642.
http://dx.doi.org/10.1056/NEJM198612253152603

[11]   Amedei, A., Prisco, D. and D’elios, M.M. (2012) Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies. International Journal of Molecular Sciences, 13, 13438-13460.
http://dx.doi.org/10.3390/ijms131013438

[12]   Bower, J.E., Ganz, P.A., Aziz, N. and Fahey, J.L. (2002) Fatigue and Proinflammatory Cytokine Activity in Breast Cancer Survivors. Psychosomatic Medicine, 64, 604-611.
http://dx.doi.org/10.1097/00006842-200207000-00010

[13]   Kerr, J.R., Barah, F., Mattey, D.L., Laing, I., Hopkins, S.J., Hutchinson, I.V., et al. (2001) Circulating Tumour Necrosis Factor-α and Interferon-γ Are Detectable during Acute and Convalescent Parvovirus B19 Infection and Are Associated with Prolonged and Chronic Fatigue. Journal of General Virology, 82, 3011-3019.
http://dx.doi.org/10.1099/0022-1317-82-12-3011

[14]   Kurzrock, R. (2001) The Role of Cytokines in Cancer-Related Fatigue. Cancer, 92, 1684-1688.
http://dx.doi.org/10.1002/1097-0142(20010915)92:6+<1684::AID-CNCR1497>3.0.CO;2-Z

[15]   Patarca, R. (2001) Cytokines and Chronic Fatigue Syndrome. Annals of the New York Academy of Sciences, 933, 185-200.
http://dx.doi.org/10.1111/j.1749-6632.2001.tb05824.x

[16]   Vgontzas, A.N., Papanicolaou, D.A., Bixler, E.O., Hopper, K., Lotsikas, A., Lin, H.-M., et al. (2000) Sleep Apnea and Daytime Sleepiness and Fatigue: Relation to Visceral Obesity, Insulin Resistance, and Hypercytokinemia. The Journal of Clinical Endocrinology & Metabolism, 85, 1151-1158.
http://dx.doi.org/10.1210/jcem.85.3.6484

[17]   Vgontzas, A.N. and Chrousos, G.P. (2002) Sleep, the Hypothalamic-Pituitary-Adrenal Axis, and Cytokines: Multiple Interactions and Disturbances in Sleep Disorders. Endocrinology and Metabolism Clinics of North America, 31, 15-36.
http://dx.doi.org/10.1016/S0889-8529(01)00005-6

[18]   Romagnani, S. (2008) Human Th17 Cells. Arthritis Research & Therapy, 10, 206.
http://dx.doi.org/10.1186/ar2392

[19]   Gaffen, S.L. (2008) An Overview of IL-17 Function and Signaling. Cytokine, 43, 402-407.
http://dx.doi.org/10.1016/j.cyto.2008.07.017

[20]   Walsh, M.J. and Tourtellotte, W.W. (1986) Temporal Invariance and Clonal Uniformity of Brain and Cerebrospinal IgG, IgA, and IgM in Multiple Sclerosis. The Journal of Experimental Medicine, 163, 41-53.
http://dx.doi.org/10.1084/jem.163.1.41

[21]   Alter, A., Duddy, M., Hebert, S., Biernacki, K., Prat, A., Antel, J.P., et al. (2003) Determinants of Human B Cell Migration across Brain Endothelial Cells. The Journal of Immunology, 170, 4497-4505.
http://dx.doi.org/10.4049/jimmunol.170.9.4497

[22]   Ransohoff, R.M., Kivisäkk, P. and Kidd, G. (2003) Three or More Routes for Leukocyte Migration into the Central Nervous System. Nature Reviews Immunology, 3, 569-581.
http://dx.doi.org/10.1038/nri1130

[23]   Bystry, R.S., Aluvihare, V., Welch, K.A., Kallikourdis, M. and Betz, A.G. (2001) B Cells and Professional APCs Recruit Regulatory T Cells via CCL4. Nature Immunology, 2, 1126-1132.

[24]   Donlon, T., Krensky, A., Wallace, M., Collins, F., Lovett, M. and Clayberger, C. (1990) Localization of a Human T-Cell-Specific Gene, RANTES (D17S136E), to Chromosome 17q11. 2-q12. Genomics, 6, 548-553.
http://dx.doi.org/10.1016/0888-7543(90)90485-D

[25]   Zuvich, R., McCauley, J.L., Pericak-Vance, M.A. and Haines, J., Eds. (2009) Genetics and Pathogenesis of Multiple Sclerosis. Seminars in Immunology, 21, 328-333.
http://dx.doi.org/10.1016/j.smim.2009.08.003

[26]   Oksenberg, J.R. and Baranzini, S.E. (2010) Multiple Sclerosis Genetics—Is the Glass Half Full, or Half Empty? Nature Reviews Neurology, 6, 429-437.
http://dx.doi.org/10.1038/nrneurol.2010.91

[27]   Steinman, L. and Zamvil, S. (2003) Transcriptional Analysis of Targets in Multiple Sclerosis. Nature Reviews Immunology, 3, 483-492.
http://dx.doi.org/10.1038/nri1108

[28]   Mariño, K., Bones, J., Kattla, J.J. and Rudd, P.M. (2010) A Systematic Approach to Protein Glycosylation Analysis: A Path through the Maze. Nature Chemical Biology, 6, 713-723.
http://dx.doi.org/10.1038/nchembio.437

[29]   Sospedra, M. and Martin, R. (2005) Immunology of Multiple Sclerosis. Annual Review of Immunology, 23, 683-747.
http://dx.doi.org/10.1146/annurev.immunol.23.021704.115707

[30]   Pérez-Nievas, B.G., García-Bueno, B., Madrigal, J.L. and Leza, J.C. (2010) Chronic Immobilisation Stress Ameliorates Clinical Score and Neuroinflammation in a MOG-Induced EAE in Dark Agouti Rats: Mechanisms Implicated. Journal of Neuroinflammation, 7, 60.
http://dx.doi.org/10.1186/1742-2094-7-60

[31]   Henderson, A.P., Barnett, M.H., Parratt, J.D. and Prineas, J.W. (2009) Multiple Sclerosis: Distribution of Inflammatory Cells in Newly Forming Lesions. Annals of Neurology, 66, 739-753.
http://dx.doi.org/10.1002/ana.21800

[32]   Li, J., Gran, B., Zhang, G.-X., Rostami, A. and Kamoun, M. (2005) IL-27 Subunits and Its Receptor (WSX-1) mRNAs Are Markedly Up-Regulated in Inflammatory Cells in the CNS during Experimental Autoimmune Encephalomyelitis. Journal of the Neurological Sciences, 232, 3-9.
http://dx.doi.org/10.1016/j.jns.2004.12.013

[33]   Irving, S.G., Zipfel, P.F., Balke, J., McBride, O.W., Morton, C.C., Burd, P.R., et al. (1990) Two Inflammatory Mediator Cytokine Genes Are Closely Linked and Variably Amplified on Chromosome 17q. Nucleic Acids Research, 18, 3261-3270.
http://dx.doi.org/10.1093/nar/18.11.3261

 
 
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