G-ODN protects diabetes mellitus complicated with cerebral infarction in mice model

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Danica Djergovic¹, Zhaohui Xu, Franck M. Barrat, Cao Xhing∗

   
Abstract
The objective of this study is to investigate the effects of G-ODN/Toll-like receptor 9 (TLR9) inhibitor on the mice with diabetes mellitus (DM) complicated with cerebral infarction (DMCI). The mice divided into four groups: sham, vehicle, DM + middle cerebral artery occlusion (MCAO) and DM+MCAO+G-ODN groups. Triphenyltetrazolium chloride (TTC) staining used to measurement of infarction area, dry-wet method for investigate cerebral water content, and western blotting for detecting the expressions of TLR9 signaling pathway. After streptozotocin (STZ) injection, when compared with the sham group, blood glucose in the other two groups was increased greatly, while blood glucose in the DM+MCAO+G-ODN group was lower than that in the DM + MCAO group. Furthermore, there is a significant decrease in SOD activity, increase in MDA, apoptosis, expressions of Bcl-2, Bax, caspase-3, proinflammatory cytokines and TLR9 proteins in mice model groups. Compared with the DM + MCAO group, mice in the DM+MCAO+G-ODN group had an evident increase in SOD activity and an obvious decrease in MDA content. Additionally, mice in the DM + MCAO group had more infarct volume ratio and cerebral water content. Mice in DM + MCAO group had the most apoptotic cells. While comparing with the DM + MCAO group, expressions of Bcl-2, Bax, caspase-3, TNF-α, IL-1β and TLR4 proteins were decreased in the DM+MCAO+G-ODN group. Our study confirmed that inhibition of TLR9 signaling pathway may protects neuronal cells in diabetes mellitus complicated with cerebral infarction.

Keywords: TLR9; Neuronal cells; G-ODN; Diabetes mellitus

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References

  1. Stegmayr B, Asplud K. Diabetes as a risk factor for stroke: a population perspective. Diabetologia 1995;38:1061-1068. [CrossRef Medline]
  2. Riddle MC, Hart J. Hyperglycemia recognised and unrecognised risk factor stroke and transient ischemic attacks. Stroke 1982;13:356-359. [Abstract/FREE Full Text]
  3. Cox NH, Lorians JW. The prognostic value of blood glucose and glycosylated estimation in persons with stroke. Postgrad Med J 1986;62:7-10. [Abstract/FREE Full Text]
  4. Letho S, Rönnemaa T, Pyörälä K, Laakso M. Predictors of stroke in middle-aged patients with non-insulin-dependent diabetes. Stroke 1996;27:63-68. [Abstract/FREE Full Text]
  5. Howard BV, Van Horn L, Hsia J, et al. Low-fat dietary pattern and risk of cardiovascular disease: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295:655-666. [CrossRefMedline]
  6. Wong FS, Janeway CA Jr. The role of CD4 and CD8 T cells in type I diabetes in the NOD mouse. Res Immunol 1997;148:327-332. [PubMed]
  7. Anderson MS, Bluestone JA. The NOD mouse: a model of immune dysregulation. Annu Rev Immunol 2005;23:447-485. [PubMed]
  8. Papadimitraki ED, Bertsias GK, Boumpas DT. Toll like receptors and autoimmunity: a critical appraisal. J Autoimmun 2007;29:310-318. [PubMed]
  9. Allam R, Anders HJ. The role of innate immunity in autoimmune tissue injury. Curr Opin Rheumatol 2008;20:538-544. [PubMed]
  10. Brentano F, Kyburz D, Gay S. Toll-like receptors and rheumatoid arthritis. Methods Mol Biol 2009;517:329-343. [PubMed]
  11. Takeshita F, Leifer CA, Gursel I, et al. Cutting edge: Role of Toll-like receptor 9 in CpG DNA-induced activation of human cells. J Immunol 2001;167:3555-3558. [PubMed]
  12. Kaisho T, Akira S. Dendritic-cell function in Toll-like receptor- and MyD88-knockout mice. Trends Immunol 2001;22:78-83. [PubMed]
  13. Wong FS, Hu C, Zhang L, et al. The role of Toll-like receptors 3 and 9 in the development of autoimmune diabetes in NOD mice. Ann N Y Acad Sci 2008;1150:146-148. [PubMed]
  14. Yegutkin GG. Nucleotide- and nucleoside-converting ectoenzymes: Important modulators of purinergic signalling cascade. Biochim Biophys Acta 2008;1783:673-694. [PubMed]
  15. Hasegawa T, Bouis D, Liao H, Visovatti SH, Pinsky DJ. Ecto-5’ nucleotidase (CD73)-mediated adenosine generation and signaling in murine cardiac allograft vasculopathy. Circ Res 2008;103:1410-1421. [PMC free article] [PubMed]
  16. Reutershan J, Vollmer I, Stark S, Wagner R, Ngamsri KC, Eltzschig HK. Adenosine and inflammation: CD39 and CD73 are critical mediators in LPS-induced PMN trafficking into the lungs. FASEB J 2009;23:473-482. [PubMed]
  17.  Mandapathil M, Hilldorfer B, Szczepanski MJ, et al. Generation and accumulation of immunosuppressive adenosine by human CD4+CD25highFOXP3+ regulatory T cells. J Biol Chem 2010;285:7176-7186. [PMC free article] [PubMed]
  18. Kawai T, Adachi O, Ogawa T, Takeda K, Akira S. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 1999;11:115-122. [PubMed]
  19.  Hoebe K, Du X, Georgel P, et al. Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 2003;424:743-748. [PubMed]
  20. Aumeunier A, Grela F, Ramadan A, et al. Systemic Toll-like receptor stimulation suppresses experimental allergic asthma and autoimmune diabetes in NOD mice. PLoS One 2010;5:e11484. [PMC free article] [PubMed]
  21. Wiersinga WJ. Current insights in sepsis: from pathogenesis to new treatment targets. Curr Opin Crit Care 2011;17:480-486. [PubMed]
  22. Lartigue A, Colliou N, Calbo S, et al. Critical role of TLR2 and TLR4 in autoantibody production and glomerulonephritis in lpr mutation-induced mouse lupus. J Immunol 2009;183(10):6207-16. [PubMed]
  23. Capolunghi F, Rosado MM, Cascioli S, et al. Pharmacological inhibition of TLR9 activation blocks autoantibody production in human B cells from SLE patients. Rheumatology (Oxford) 2010;49(12):2281-9. [PubMed]
  24. Guiducci C, Gong M, Xu Z, et al. TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus. Nature 2010;465(7300):937-41. [PMC free article] [PubMed]
  25. Kobayashi K, Hernandez LD, Galán JE, et al. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 2002;110(2):191-202. [PubMed]
  26. Dulay AT, Buhimschi CS, Zhao G, et al. Soluble TLR2 is present in human amniotic fluid and modulates the intraamniotic inflammatory response to infection. J Immunol 2009;182(11):7244-53. [PubMed]
  27. Colonna M. TLR pathways and IFN-regulatory factors: to each its own. Eur J Immunol 2007;37(2):306-9. [PubMed]
  28.  Kawai T, Sato S, Ishii KJ, et al. Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat Immunol 2004;5(10):1061-8. [PubMed]
  29. O'Neill LA, Bowie AG. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol 2007;7(5):353-64. [PubMed]
  30. Hennessy EJ, Parker AE, O'Neill LA. Targeting Toll-like receptors: emerging therapeutics? Nat Rev Drug Discov 2010;9(4):293-307. [PubMed]
  31. Roelofs MF, Joosten LA, Abdollahi-Roodsaz S, et al. The expression of toll-like receptors 3 and 7 in rheumatoid arthritis synovium is increased and costimulation of toll-like receptors 3, 4, and 7/8 results in synergistic cytokine production by dendritic cells. Arthritis Rheum 2005;52(8):2313-22. [PubMed]

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DOI: 10.18081/2333-5106/016-11/480-504

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Research Article
American Journal of BioMedicine Volume 4, Issue 11, pages 480-504
Received June 12, 2016; accepted October 24, 2016; published November 27, 2016

How to cite this article
Djergovic D, Xu Z, Barrat FM, Xhing C. G-ODN protects diabetes mellitus complicated with cerebral infarction in mice model. American Journal of BioMedicine 2016;4(11):480-504.

Article outline
1. Abstract
2. Keywords
3. Introduction
4. Materials and Methods
5. Results
6. Discussions
7. Acknowledgements
8. References

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