Co Expression of GMFβ, IL33, CCL2 and SDF1 Genes in the Acute Stage of Toxoplasmosis in Mice Model and Relation for Neuronal Impairment
Abstract
Background: Toxoplasma gondii is an obligate intracellular parasite that migrates through macrophages or dendritic cells to neurons and nerve cells. Glia Maturation Factor (GMF) is a pre-inflammatory protein that is expressed in the central nervous system (CNS). GMFβ expression is related to IL33 and CCL2 and SDF1 in some neurodegenerative diseases. According to the importance of GMFβ in neurodegenerative diseases and its association with IL33, CCL2 and SDF1 genes, this study was designed to determine the level of expression of these genes in the brains of mice with acute toxoplasmosis.
Methods: Tachyzoites of T. gondii RH strains were injected to 5 Swiss Albino mice. At the same time, healthy mice were inoculated with the Phosphate-buffered saline (PBS). Their brains were removed and kept at -70 oC in order to RNA extraction, cDNA syntheses and Real Time PCR performance. The level of gene expression was investigated with SYBR Green Quantitative Real-Time PCR.
Results: GMFβ gene expression increased significantly (P=0.003) 3.26 fold in Toxoplasma infected mice in comparison to the control. GMFβ gene expression was associated with increased expression level of IL33, CCL2, and SDF1 genes.
Conclusion: Considering the prominent role of GMFβ in CNS as well as the immune system, the elevation of GMFβ, IL33, CCL2 and SDF1 genes expression in the early stage of toxoplasmosis is associated with the occurrence of neuropathological alterations. Detection of these genes as an indication of brain damage in the early stages of Toxoplasma infection can prevent neurodegenerative disorders following acquired toxoplasmosis.
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9. Feng C, Wang X, Liu T, et al. Expression of CCL2 and its receptor in activation and migration of microglia and monocytes induced by photoreceptor apoptosis. Mol Vis. 2017;23:765-777.
10. Sanseverino I, Rinaldi AO, Purificato C, et al. CCL2 induction by 1, 25 (OH) 2D3 in dendritic cells from healthy donors and multiple sclerosis patients. J Steroid Biochem Mol Biol. 2014;144:102-5: doi: 10.1016/j.jsbmb.2013.10.018
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12. Sun Y, Dai M, Wang Y, et al. Neuroprotection and sensorimotor functional improvement by curcumin after intracerebral hemorrhage in mice. J Neurotrauma. 2011;28(12):2513-21.
13. Chomczynski P, Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction: twenty-something years on. Nature Protocols. 2006;1(2):581-585.
14. Karimi Dermani F, Saidijam M, Amini R, et al. Resveratrol inhibits proliferation, invasion, and epithelial–mesenchymal transition by increasing miR‐200c expression in HCT‐116 colorectal cancer cells. J Cell Biochem. 2017;118(6):1547-1555.
15. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25(4):402-8. doi: doi:10.1006/meth.2001.
16. Kempuraj D, Khan MM, Thangavel R, et al. Glia maturation factor induces interleukin-33 release from astrocytes: implications for neurodegenerative diseases. J Neuroimmune Pharmacol. 2013;8(3):643-50. doi: 10.1007/s11481-013-9439-7.
17. Dincel GC. First description of enhanced expression of glia maturation factor-beta in experimental toxoplasmic encephalitis. J Int Med Res. 2017;45(6):1670-1679. doi: 10.177/0300060517700320.
18. Kaimori J-y, Takenaka M, Nakajima H, et al. Induction of glia maturation factor-β in proximal tubular cells leads to vulnerability to oxidative injury through the p38 pathway and changes in antioxidant enzyme activities. J Biol Chem. 2003;278(35):33519-27. doi: 10.1074/jbc.M301552200.
19. Khan MM, Kempuraj D, Zaheer S, et al. Glia maturation factor deficiency suppresses 1-methyl-4-phenylpyridinium-induced oxidative stress in astrocytes. J Mol Neurosci. 2014;53(4):590-599. doi: 10.1007/s12031-013-0225-z.
20. Zaheer A, Yang B, Cao X, et al. Decreased copper–zinc superoxide dismutase activity and increased resistance to oxidative stress in glia maturation factor–null astrocytes. Neurochem Res. 2004;29(8):1473-80. doi: 10.023/b:nere.0000029558.82943.00.
21. Flegr J. Schizophrenia and Toxoplasma gondii: an undervalued association? Expert Rev Anti Infect Ther. 2015;13(7):817-20. doi: 10.1586/14787210.2015.1051033.
22. Sutterland A, Fond G, Kuin A, et al. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta‐analysis. Acta Psychiatr Scand. 2015;132(3):161-79. doi: 10.1111/acps.12423.
23. Bernstein H-G, Bogerts B, Keilhoff G. The many faces of nitric oxide in schizophrenia. A review. Schizophr Res. 2005;78(1):69-86. doi: 10.1016/j.schres.2005.05.019.
24. Yanik M, Vural H, Kocyigit A, et al. Is the arginine-nitric oxide pathway involved in the pathogenesis of schizophrenia? Neuropsychobiology. 2003;47(2):61-5. doi: 10.1159/000070010.
25. Dincel GC, Atmaca HT. Increased expressions of ADAMTS‐13 and apoptosis contribute to neuropathology during Toxoplasma gondii encephalitis in mice. Neuropathology. 2016;36(3):211-26. doi: 10.1111/neup.12263.
26. Mukherjee S, Mahadik SP, Scheffer R, et al . Impaired antioxidant defense at the onset of psychosis. Schizophr Res. 1996;19(1):19-26.
27. Stolmeier D, Thangavel R, Anantharam P, et al. Glia maturation factor expression in hippocampus of human Alzheimer’s disease. Neurochem Res. 2013;38(8):1580-9. doi: 10.007/s11064-013-1059-3.
28. Lee SC, Liu W, Brosnan CF, et al. GM‐CSF promotes proliferation of human fetal and adult microglia in primary cultures. Glia. 1994;12(4):309-18. doi: 10.1002/glia.440120407.
29. Tarkowski E, Wallin A, Regland B, et al . Local and systemic GM‐CSF increase in Alzheimer's disease and vascular dementia. Acta Neurol Scand. 2001;103(3):166-74. doi: 10.1034/j.600-0404.2001.103003166.x.
30. Farfara D, Lifshitz V, Frenkel D. Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease. J Cell Mol Med. 2008;12(3):762-80. doi: 10.1111/j.582-4934.2008.00314.x.
31. Miljković D, Timotijević G, Stojković MM. Astrocytes in the tempest of multiple sclerosis. FEBS Lett. 2011;585(23):3781-8. doi: 10.1016/j.febslet.2011.03.047.
32. Galimberti D, Fenoglio C, Lovati C, et al. Serum MCP-1 levels are increased in mild cognitive impairment and mild Alzheimer's disease. Neurobiol Aging. 2006;27(12):1763-8. doi: 10.016/j.neurobiolaging.2005.10.007.
33. Conductier G, Blondeau N, Guyon A, et al. The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases. J Neuroimmunol. 2010;224(1-2):93-100. doi: 10.1016/j.jneuroim.2010.05.010.
34. Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004;10(8):858-64. doi: 10.1038/nm75.
35. Liu F, Mccullough LD. Inflammatory responses in hypoxic ischemic encephalopathy. Acta Pharmacol Sin. 2013;34(9):1121-30. doi: 10.038/aps.2013.89.
36. Hill D, Dubey J. Toxoplasma gondii: transmission, diagnosis and prevention. Clin Microbiol Infect. 2002;8(10):634-40. doi: 10.1046/j.469-0691.2002.00485.x.
37. Azin H, Vazirinejad R, Ahmadabadi BN, et al. The SDF-1 3′ a genetic variation of the chemokine SDF-1α (CXCL12) in parallel with its increased circulating levels is associated with susceptibility to MS: a study on Iranian multiple sclerosis patients. J Mol Neurosci. 2012;47(3):431-6. doi: 10.1007/s12031-011-9672-6.
38. Cheng X, Wang H, Zhang X, et al. The role of SDF-1/CXCR4/CXCR7 in neuronal regeneration after cerebral ischemia. Front Neurosci. 2017;11:590. doi: 10.3389/fnins.2017.00590.
39. Hassanshahi G, Arababadi MK, Khoramdelazad H, et al. Assessment of CXCL12 (SDF-1α) polymorphisms and its serum level in posttransfusion occult HBV-infected patients in Southeastern Iran. Arch Med Res. 2010;41(5):338-42. doi: 10.1016/j.arcmed.2010.07.001.
40. Skaper SD, Giusti P, Facci L. Microglia and mast cells: two tracks on the road to neuroinflammation. FASEB J. 2012;26(8):3103-17. doi: 10.1096/fj.11-197194.
41. Dinarello CA. Anti-inflammatory agents: present and future. Cell. 2010;140(6):935-50. doi: 10.1016/j.cell.2010.02.043.
42. Shamim D, Laskowski M. Inhibition of inflammation mediated through the tumor necrosis factor α biochemical pathway can lead to favorable outcomes in Alzheimer disease. J Cent Nerv Syst Dis. 2017; 9:1179573517722512. doi: 10.1177/1179573517722512.
43. Tong X, Lu F. IL-33/ST2 involves the immunopathology of ocular toxoplasmosis in murine model. Parasitol Res. 2015;114(5):1897-905. doi: 10.007/s00436-015-4377-3.
2. Zaheer A, Zaheer S, Sahu SK, et al. A novel role of glia maturation factor: induction of granulocyte‐macrophage colony‐stimulating factor and pro‐inflammatory cytokines. J Neurochem. 2007;101(2):364-76.
3. Yasuoka S, Kawanokuchi J, Parajuli B, et al. Production and functions of IL-33 in the central nervous system. Brain Res. 2011;1385:8-17. doi: 0.1016/j.brainres.2011.02.045.
4. Chapuis J, Hot D, Hansmannel F, et al. Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease. Mol Psychiatry. 2009;14(11):1004-16. doi: 10.38/mp.2009.10.
5. Cui L, Qu H, Xiao T, et al. Stromal cell-derived factor-1 and its receptor CXCR4 in adult neurogenesis after cerebral ischemia. Restor Neurol Neurosci. 2013;31(3):239-51. doi: 10.3233/RNN-120271.
6. Tiveron M-C, Cremer H. CXCL12/CXCR4 signalling in neuronal cell migration. Curr Opin Neurobiol. 2008;18(3):237-44. doi:10.1016/j.conb.2008.06.004.
7. Szepesi Z, Manouchehrian O, Bachiller S, et al. Bidirectional microglia–neuron communication in health and disease. Front Cell Neurosci. 2018;12:323. doi:10.3389/fncel.2018.00323.
8. Westin K, Buchhave P, Nielsen H, et al . CCL2 is associated with a faster rate of cognitive decline during early stages of Alzheimer's disease. PLoS One. 2012; 7(1):doi:10.1371/journal.pone.0030525.
9. Feng C, Wang X, Liu T, et al. Expression of CCL2 and its receptor in activation and migration of microglia and monocytes induced by photoreceptor apoptosis. Mol Vis. 2017;23:765-777.
10. Sanseverino I, Rinaldi AO, Purificato C, et al. CCL2 induction by 1, 25 (OH) 2D3 in dendritic cells from healthy donors and multiple sclerosis patients. J Steroid Biochem Mol Biol. 2014;144:102-5: doi: 10.1016/j.jsbmb.2013.10.018
11. Syn G, Anderson D, Blackwell JM, et al. Epigenetic dysregulation of host gene expression in Toxoplasma infection with specific reference to dopamine and amyloid pathways. Infect Genet Evol. 2018;65:159-62. doi: 10.1016/j.meegid.2018.07.034.
12. Sun Y, Dai M, Wang Y, et al. Neuroprotection and sensorimotor functional improvement by curcumin after intracerebral hemorrhage in mice. J Neurotrauma. 2011;28(12):2513-21.
13. Chomczynski P, Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction: twenty-something years on. Nature Protocols. 2006;1(2):581-585.
14. Karimi Dermani F, Saidijam M, Amini R, et al. Resveratrol inhibits proliferation, invasion, and epithelial–mesenchymal transition by increasing miR‐200c expression in HCT‐116 colorectal cancer cells. J Cell Biochem. 2017;118(6):1547-1555.
15. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25(4):402-8. doi: doi:10.1006/meth.2001.
16. Kempuraj D, Khan MM, Thangavel R, et al. Glia maturation factor induces interleukin-33 release from astrocytes: implications for neurodegenerative diseases. J Neuroimmune Pharmacol. 2013;8(3):643-50. doi: 10.1007/s11481-013-9439-7.
17. Dincel GC. First description of enhanced expression of glia maturation factor-beta in experimental toxoplasmic encephalitis. J Int Med Res. 2017;45(6):1670-1679. doi: 10.177/0300060517700320.
18. Kaimori J-y, Takenaka M, Nakajima H, et al. Induction of glia maturation factor-β in proximal tubular cells leads to vulnerability to oxidative injury through the p38 pathway and changes in antioxidant enzyme activities. J Biol Chem. 2003;278(35):33519-27. doi: 10.1074/jbc.M301552200.
19. Khan MM, Kempuraj D, Zaheer S, et al. Glia maturation factor deficiency suppresses 1-methyl-4-phenylpyridinium-induced oxidative stress in astrocytes. J Mol Neurosci. 2014;53(4):590-599. doi: 10.1007/s12031-013-0225-z.
20. Zaheer A, Yang B, Cao X, et al. Decreased copper–zinc superoxide dismutase activity and increased resistance to oxidative stress in glia maturation factor–null astrocytes. Neurochem Res. 2004;29(8):1473-80. doi: 10.023/b:nere.0000029558.82943.00.
21. Flegr J. Schizophrenia and Toxoplasma gondii: an undervalued association? Expert Rev Anti Infect Ther. 2015;13(7):817-20. doi: 10.1586/14787210.2015.1051033.
22. Sutterland A, Fond G, Kuin A, et al. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta‐analysis. Acta Psychiatr Scand. 2015;132(3):161-79. doi: 10.1111/acps.12423.
23. Bernstein H-G, Bogerts B, Keilhoff G. The many faces of nitric oxide in schizophrenia. A review. Schizophr Res. 2005;78(1):69-86. doi: 10.1016/j.schres.2005.05.019.
24. Yanik M, Vural H, Kocyigit A, et al. Is the arginine-nitric oxide pathway involved in the pathogenesis of schizophrenia? Neuropsychobiology. 2003;47(2):61-5. doi: 10.1159/000070010.
25. Dincel GC, Atmaca HT. Increased expressions of ADAMTS‐13 and apoptosis contribute to neuropathology during Toxoplasma gondii encephalitis in mice. Neuropathology. 2016;36(3):211-26. doi: 10.1111/neup.12263.
26. Mukherjee S, Mahadik SP, Scheffer R, et al . Impaired antioxidant defense at the onset of psychosis. Schizophr Res. 1996;19(1):19-26.
27. Stolmeier D, Thangavel R, Anantharam P, et al. Glia maturation factor expression in hippocampus of human Alzheimer’s disease. Neurochem Res. 2013;38(8):1580-9. doi: 10.007/s11064-013-1059-3.
28. Lee SC, Liu W, Brosnan CF, et al. GM‐CSF promotes proliferation of human fetal and adult microglia in primary cultures. Glia. 1994;12(4):309-18. doi: 10.1002/glia.440120407.
29. Tarkowski E, Wallin A, Regland B, et al . Local and systemic GM‐CSF increase in Alzheimer's disease and vascular dementia. Acta Neurol Scand. 2001;103(3):166-74. doi: 10.1034/j.600-0404.2001.103003166.x.
30. Farfara D, Lifshitz V, Frenkel D. Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease. J Cell Mol Med. 2008;12(3):762-80. doi: 10.1111/j.582-4934.2008.00314.x.
31. Miljković D, Timotijević G, Stojković MM. Astrocytes in the tempest of multiple sclerosis. FEBS Lett. 2011;585(23):3781-8. doi: 10.1016/j.febslet.2011.03.047.
32. Galimberti D, Fenoglio C, Lovati C, et al. Serum MCP-1 levels are increased in mild cognitive impairment and mild Alzheimer's disease. Neurobiol Aging. 2006;27(12):1763-8. doi: 10.016/j.neurobiolaging.2005.10.007.
33. Conductier G, Blondeau N, Guyon A, et al. The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases. J Neuroimmunol. 2010;224(1-2):93-100. doi: 10.1016/j.jneuroim.2010.05.010.
34. Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004;10(8):858-64. doi: 10.1038/nm75.
35. Liu F, Mccullough LD. Inflammatory responses in hypoxic ischemic encephalopathy. Acta Pharmacol Sin. 2013;34(9):1121-30. doi: 10.038/aps.2013.89.
36. Hill D, Dubey J. Toxoplasma gondii: transmission, diagnosis and prevention. Clin Microbiol Infect. 2002;8(10):634-40. doi: 10.1046/j.469-0691.2002.00485.x.
37. Azin H, Vazirinejad R, Ahmadabadi BN, et al. The SDF-1 3′ a genetic variation of the chemokine SDF-1α (CXCL12) in parallel with its increased circulating levels is associated with susceptibility to MS: a study on Iranian multiple sclerosis patients. J Mol Neurosci. 2012;47(3):431-6. doi: 10.1007/s12031-011-9672-6.
38. Cheng X, Wang H, Zhang X, et al. The role of SDF-1/CXCR4/CXCR7 in neuronal regeneration after cerebral ischemia. Front Neurosci. 2017;11:590. doi: 10.3389/fnins.2017.00590.
39. Hassanshahi G, Arababadi MK, Khoramdelazad H, et al. Assessment of CXCL12 (SDF-1α) polymorphisms and its serum level in posttransfusion occult HBV-infected patients in Southeastern Iran. Arch Med Res. 2010;41(5):338-42. doi: 10.1016/j.arcmed.2010.07.001.
40. Skaper SD, Giusti P, Facci L. Microglia and mast cells: two tracks on the road to neuroinflammation. FASEB J. 2012;26(8):3103-17. doi: 10.1096/fj.11-197194.
41. Dinarello CA. Anti-inflammatory agents: present and future. Cell. 2010;140(6):935-50. doi: 10.1016/j.cell.2010.02.043.
42. Shamim D, Laskowski M. Inhibition of inflammation mediated through the tumor necrosis factor α biochemical pathway can lead to favorable outcomes in Alzheimer disease. J Cent Nerv Syst Dis. 2017; 9:1179573517722512. doi: 10.1177/1179573517722512.
43. Tong X, Lu F. IL-33/ST2 involves the immunopathology of ocular toxoplasmosis in murine model. Parasitol Res. 2015;114(5):1897-905. doi: 10.007/s00436-015-4377-3.
| Files | ||
| Issue | Vol 16 No 3 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v16i3.7096 | |
| Keywords | ||
| Toxoplasma gondii; Glia Maturation Factor Interleukin-33 Chemokine CCL2 | ||
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How to Cite
1.
Najafi M, Amini R, Maghsood AH, Fallah M, Foroughi-Parvar F. Co Expression of GMFβ, IL33, CCL2 and SDF1 Genes in the Acute Stage of Toxoplasmosis in Mice Model and Relation for Neuronal Impairment. Iran J Parasitol. 2021;16(3):426-434.
