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Silencing of miR155 Promotes the Production of Inflammatory Mediators in Guillain–Barré Syndrome In Vitro

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Abstract

MicroRNA-155 (miR155) has been demonstrated as a central regulator of immune responses induced by inflammatory mediators. Previous studies suggest that miR155 may play adverse effects in various diseases. We hereby explored the roles of miR155 in the pathogenesis of Guillain–Barré syndrome (GBS). Peripheral blood mononuclear cells (PBMCs) were separated from GBS patients and healthy controls. Expression of miR155 in PBMCs was detected by quantitative PCR. An inhibitor of miR155 was transfected into the cultured PBMCs and the GBS-related cytokines were detected. Significantly, our study demonstrated that miR155 was downregulated in PBMCs from GBS patients and silencing of miR155 profoundly promoted the production of Th1-type cytokines in vitro. Our data effectively demonstrate a protective role of miR155 in GBS, which suggests that miR155 may be a promising target for the therapy of the disease.

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References

  1. Hughes, R.A., R.D. Hadden, N.A. Gregson, and K.J. Smith. 1999. Pathogenesis of Guillain–Barre syndrome. Journal of Neuroimmunology 100: 74–97.

    Article  PubMed  CAS  Google Scholar 

  2. Nyati, K.K., K.N. Prasad, A. Rizwan, A. Verma, and V.K. Paliwal. 2011. TH1 and TH2 response to Campylobacter jejuni antigen in Guillain–Barre syndrome. Archives of Neurology 68: 445–452.

    Article  PubMed  Google Scholar 

  3. van Doorn, P.A., L. Ruts, and B.C. Jacobs. 2008. Clinical features, pathogenesis, and treatment of Guillain–Barre syndrome. Lancet Neurology 7: 939–950.

    Article  PubMed  Google Scholar 

  4. Hughes, R.A., A.V. Swan and P.A. van Doorn. 2010. Intravenous immunoglobulin for Guillain–Barre syndrome. The Cochrane Database of Systematic Reviews CD002063.

  5. van Doorn, P.A., K. Kuitwaard, C. Walgaard, R. van Koningsveld, L. Ruts, and B.C. Jacobs. 2010. IVIG treatment and prognosis in Guillain–Barre syndrome. Journal of Clinical Immunology 30(Suppl 1): S74–S78.

    Article  PubMed  Google Scholar 

  6. Alshekhlee, A., Z. Hussain, B. Sultan, and B. Katirji. 2008. Guillain–Barre syndrome: incidence and mortality rates in US hospitals. Neurology 70: 1608–1613.

    Article  PubMed  Google Scholar 

  7. Willison, H.J., and N. Yuki. 2002. Peripheral neuropathies and anti-glycolipid antibodies. Brain 125: 2591–2625.

    Article  PubMed  Google Scholar 

  8. Hafer-Macko, C.E., K.A. Sheikh, C.Y. Li, T.W. Ho, D.R. Cornblath, G.M. McKhann, A.K. Asbury, and J.W. Griffin. 1996. Immune attack on the Schwann cell surface in acute inflammatory demyelinating polyneuropathy. Annals of Neurology 39: 625–635.

    Article  PubMed  CAS  Google Scholar 

  9. Lee, R.C., R.L. Feinbaum, and V. Ambros. 1993. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75: 843–854.

    Article  PubMed  CAS  Google Scholar 

  10. O'Neill, L.A., F.J. Sheedy, and C.E. McCoy. 2011. MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nature Reviews Immunology 11: 163–175.

    Article  PubMed  Google Scholar 

  11. Ha, T.Y. 2011. The role of microRNAs in regulatory T cells and in the immune response. Immune Network 11: 11–41.

    Article  PubMed  Google Scholar 

  12. Tam, W., D. Ben-Yehuda, and W.S. Hayward. 1997. bic, a novel gene activated by proviral insertions in avian leukosis virus-induced lymphomas, is likely to function through its noncoding RNA. Molecular and Cellular Biology 17: 1490–1502.

    PubMed  CAS  Google Scholar 

  13. Thai, T.H., D.P. Calado, S. Casola, K.M. Ansel, C. Xiao, Y. Xue, A. Murphy, D. Frendewey, D. Valenzuela, J.L. Kutok, M. Schmidt-Supprian, N. Rajewsky, G. Yancopoulos, A. Rao, and K. Rajewsky. 2007. Regulation of the germinal center response by microRNA-155. Science 316: 604–608.

    Article  PubMed  CAS  Google Scholar 

  14. Rodriguez, A., E. Vigorito, S. Clare, M.V. Warren, P. Couttet, D.R. Soond, S. van Dongen, R.J. Grocock, P.P. Das, E.A. Miska, D. Vetrie, K. Okkenhaug, A.J. Enright, G. Dougan, M. Turner, and A. Bradley. 2007. Requirement of bic/microRNA-155 for normal immune function. Science 316: 608–611.

    Article  PubMed  CAS  Google Scholar 

  15. Taganov, K.D., M.P. Boldin, K.J. Chang, and D. Baltimore. 2006. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proceedings of the National Academy of Sciences of the United States of America 103: 12481–12486.

    Article  PubMed  CAS  Google Scholar 

  16. Vigorito, E., K.L. Perks, C. Abreu-Goodger, S. Bunting, Z. Xiang, S. Kohlhaas, P.P. Das, E.A. Miska, A. Rodriguez, A. Bradley, K.G. Smith, C. Rada, A.J. Enright, K.M. Toellner, I.C. Maclennan, and M. Turner. 2007. microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity 27: 847–859.

    Article  PubMed  CAS  Google Scholar 

  17. Wang, Y.Z., Q.H. Liang, H. Ramkalawan, Y.L. Wang, Y.F. Yang, W.B. Zhou, F.F. Tian, J. Li, and H. Yang. 2012. Expression of Toll-like receptors 2, 4 and 9 in patients with Guillain–Barre syndrome. Neuroimmunomodulation 19: 60–68.

    Article  PubMed  Google Scholar 

  18. van der Meche, F.G., and P.I. Schmitz. 1992. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain–Barre syndrome. Dutch Guillain-Barre Study Group. The New England Journal of Medicine 326: 1123–1129.

    Article  PubMed  Google Scholar 

  19. O'Connell, R.M., D. Kahn, W.S. Gibson, J.L. Round, R.L. Scholz, A.A. Chaudhuri, M.E. Kahn, D.S. Rao, and D. Baltimore. 2010. MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity 33: 607–619.

    Article  PubMed  Google Scholar 

  20. Ray, D., S. Culine, A. Tavitain, and F. Moreau-Gachelin. 1990. The human homologue of the putative proto-oncogene Spi-1: characterization and expression in tumors. Oncogene 5: 663–668.

    PubMed  CAS  Google Scholar 

  21. DeKoter, R.P., J.C. Walsh, and H. Singh. 1998. PU.1 regulates both cytokine-dependent proliferation and differentiation of granulocyte/macrophage progenitors. The EMBO Journal 17: 4456–4468.

    Article  PubMed  CAS  Google Scholar 

  22. Martinez-Nunez, R.T., F. Louafi, P.S. Friedmann, and T. Sanchez-Elsner. 2009. MicroRNA-155 modulates the pathogen binding ability of dendritic cells (DCs) by down-regulation of DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN). The Journal of Biological Chemistry 284: 16334–16342.

    Article  PubMed  CAS  Google Scholar 

  23. Ekerfelt, C., C. Dahle, R. Weissert, M. Kvarnstrom, T. Olsson, and J. Ernerudh. 2001. Transfer of myelin-specific cells deviated in vitro towards IL-4 production ameliorates ongoing experimental allergic neuritis. Clinical and Experimental Immunology 123: 112–118.

    Article  PubMed  CAS  Google Scholar 

  24. Bhatheja, K., and J. Field. 2006. Schwann cells: origins and role in axonal maintenance and regeneration. The International Journal of Biochemistry & Cell Biology 38: 1995–1999.

    Article  CAS  Google Scholar 

  25. Bremer, J., T. O'Connor, C. Tiberi, H. Rehrauer, J. Weis, and A. Aguzzi. 2010. Ablation of Dicer from murine Schwann cells increases their proliferation while blocking myelination. PloS One 5: e12450.

    Article  PubMed  Google Scholar 

  26. Dugas, J.C., T.L. Cuellar, A. Scholze, B. Ason, A. Ibrahim, B. Emery, J.L. Zamanian, L.C. Foo, M.T. McManus, and B.A. Barres. 2010. Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination. Neuron 65: 597–611.

    Article  PubMed  CAS  Google Scholar 

  27. Kominato, Y., D. Galson, W.R. Waterman, A.C. Webb, and P.E. Auron. 1995. Monocyte expression of the human prointerleukin 1 beta gene (IL1B) is dependent on promoter sequences which bind the hematopoietic transcription factor Spi-1/PU.1. Molecular and Cellular Biology 15: 58–68.

    PubMed  CAS  Google Scholar 

  28. Fasanaro, P., S. Greco, M. Ivan, M.C. Capogrossi, and F. Martelli. 2010. microRNA: emerging therapeutic targets in acute ischemic diseases. Pharmacology and Therapeutics 125: 92–104.

    Article  PubMed  CAS  Google Scholar 

  29. Zhu, J., E. Mix, and H. Link. 1998. Cytokine production and the pathogenesis of experimental autoimmune neuritis and Guillain–Barre syndrome. Journal of Neuroimmunology 84: 40–52.

    Article  PubMed  CAS  Google Scholar 

  30. Zhu, J., E. Mix, T. Olsson, and H. Link. 1994. Cellular mRNA expression of interferon-gamma, IL-4 and transforming growth factor-beta (TGF-beta) by rat mononuclear cells stimulated with peripheral nerve myelin antigens in experimental allergic neuritis. Clinical and Experimental Immunology 98: 306–312.

    Article  PubMed  CAS  Google Scholar 

  31. Kutty, R.K., C.N. Nagineni, W. Samuel, C. Vijayasarathy, J.J. Hooks, and T.M. Redmond. 2010. Inflammatory cytokines regulate microRNA-155 expression in human retinal pigment epithelial cells by activating JAK/STAT pathway. Biochemical and Biophysical Research Communications 402: 390–395.

    Article  PubMed  CAS  Google Scholar 

  32. Ceppi, M., P.M. Pereira, I. Dunand-Sauthier, E. Barras, W. Reith, M.A. Santos, and P. Pierre. 2009. MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 106: 2735–2740.

    Article  PubMed  CAS  Google Scholar 

  33. Banerjee, A., F. Schambach, C.S. DeJong, S.M. Hammond, and S.L. Reiner. 2010. Micro-RNA-155 inhibits IFN-gamma signaling in CD4+ T cells. European Journal of Immunology 40: 225–231.

    Article  PubMed  CAS  Google Scholar 

  34. Lu, F., A. Weidmer, C.G. Liu, S. Volinia, C.M. Croce, and P.M. Lieberman. 2008. Epstein–Barr virus-induced miR-155 attenuates NF-kappaB signaling and stabilizes latent virus persistence. Journal of Virology 82: 10436–10443.

    Article  PubMed  CAS  Google Scholar 

  35. Wang, Y.Z., Q.H. Liang, H. Ramkalawan, W. Zhang, W.B. Zhou, B. Xiao, F.F. Tian, H. Yang, J. Li, Y. Zhang, and N.A. Xu. 2012. Inactivation of TLR9 by a suppressive oligodeoxynucleotides can ameliorate the clinical signs of EAN. Immunological Investigations 41: 171–182.

    Article  PubMed  CAS  Google Scholar 

  36. Tang, Y., X. Luo, H. Cui, X. Ni, M. Yuan, Y. Guo, X. Huang, H. Zhou, N. de Vries, P.P. Tak, S. Chen, and N. Shen. 2009. MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis and Rheumatism 60: 1065–1075.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Jun-Mei Zhang and Qun Liu for their technical assistance.

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The authors declare no competing financial interests.

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Correspondence to Yan-Lei Hao.

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Wang, YZ., Feng, XG., Shi, QG. et al. Silencing of miR155 Promotes the Production of Inflammatory Mediators in Guillain–Barré Syndrome In Vitro . Inflammation 36, 337–345 (2013). https://doi.org/10.1007/s10753-012-9551-5

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