Display options
Cite
Hurtado-Guerrero I, Hernáez B, Pinto-Medel MJ, et al. Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation. J Clin Med. 2020;9(4)doi: 10.3390/jcm9040959.
Hurtado-Guerrero, I., Hernáez, B., Pinto-Medel, M. J., Calonge, E., Rodriguez-Bada, J. L., Urbaneja, P., Alonso, A., Mena-Vázquez, N., Aliaga, P., Issazadeh-Navikas, S., Pavia, J., Leyva, L., Alcamí, J., Alcamí, A., Fernández, �. �., & Oliver-Martos, B. (2020). Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation. Journal of clinical medicine, 9(4), . https://doi.org/10.3390/jcm9040959
Hurtado-Guerrero, Isaac, et al. "Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation." Journal of clinical medicine vol. 9,4 (2020). doi: https://doi.org/10.3390/jcm9040959
Hurtado-Guerrero I, Hernáez B, Pinto-Medel MJ, Calonge E, Rodriguez-Bada JL, Urbaneja P, Alonso A, Mena-Vázquez N, Aliaga P, Issazadeh-Navikas S, Pavia J, Leyva L, Alcamí J, Alcamí A, Fernández Ó, Oliver-Martos B. Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation. J Clin Med. 2020 Mar 31;9(4). doi: 10.3390/jcm9040959. PMID: 32244308; PMCID: PMC7230527.
Copy Download .nbib Format: NLM
Share it on

J Clin Med. 2020 Mar 31;9(4). doi: 10.3390/jcm9040959.

Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation.

Journal of clinical medicine

Isaac Hurtado-Guerrero, Bruno Hernáez, María J Pinto-Medel, Esther Calonge, José L Rodriguez-Bada, Patricia Urbaneja, Ana Alonso, Natalia Mena-Vázquez, Pablo Aliaga, Shohreh Issazadeh-Navikas, José Pavia, Laura Leyva, José Alcamí, Antonio Alcamí, Óscar Fernández, Begoña Oliver-Martos

Affiliations

  1. Instituto de Investigación Biomédica de Málaga-IBIMA, 29009 Málaga, Spain.
  2. UGC Neurociencias. Hospital Regional Universitario de Málaga, 29010 Málaga, Spain.
  3. Red Temática de Investigación Cooperativa: Red Española de Esclerosis Múltiple REEM (RD16/0015/0010), 28049 Madrid, Spain.
  4. Neuroinflammation Unit, Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, Copenhagen Biocentre, University of Copenhagen, 2200 Copenhagen, Denmark.
  5. Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain.
  6. AIDS Immunopathology Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda 28220 Madrid, Spain.
  7. UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain.
  8. Departamento de Farmacología y Pediatría, Facultad de Medicina. Universidad de Málaga, 29010 Málaga, Spain.
  9. HIV Unit, Infectious Disease Service, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain.

PMID: 32244308 PMCID: PMC7230527 DOI: 10.3390/jcm9040959

Abstract

Soluble receptors of cytokines are able to modify cytokine activities and therefore the immune system, and some have intrinsic biological activities without mediation from their cytokines. The soluble interferon beta (IFN-ß) receptor is generated through alternative splicing of IFNAR2 and has both agonist and antagonist properties for IFN-ß, but its role is unknown. We previously demonstrated that a recombinant human soluble IFN-ß receptor showed intrinsic therapeutic efficacy in a mouse model of multiple sclerosis. Here we evaluate the potential biological activities of recombinant sIFNAR2 without the mediation of IFN-ß in human cells. Recombinant sIFNAR2 down-regulated the production of IL-17 and IFN-ɣ and reduced the cell proliferation rate. Moreover, it showed a strong antiviral activity, fully protecting the cell monolayer after being infected by the virus. Specific inhibitors completely abrogated the antiviral activity of IFN-ß, but not that of the recombinant sIFNAR2, and there was no activation of the JAK-STAT signaling pathway. Consequently, r-sIFNAR2 exerts immunomodulatory, antiproliferative and antiviral activities without IFN-ß mediation, and could be a promising treatment against viral infections and immune-mediated diseases.

Keywords: IFNAR; immunology; interferon; soluble receptors

References

  1. J Biol Chem. 2004 Apr 23;279(17):18046-53 - PubMed
  2. Hum Mol Genet. 2015 Jun 1;24(11):3192-205 - PubMed
  3. PLoS One. 2015 Mar 26;10(3):e0122672 - PubMed
  4. Expert Opin Investig Drugs. 2000 Mar;9(3):497-514 - PubMed
  5. PLoS One. 2014 Dec 05;9(12):e113840 - PubMed
  6. Methods. 2001 Dec;25(4):402-8 - PubMed
  7. Blood. 2001 Jan 15;97(2):473-82 - PubMed
  8. Bioanalysis. 2015;7(22):2869-80 - PubMed
  9. BMC Genomics. 2015 Jan 23;16:26 - PubMed
  10. Neuropharmacology. 2016 Nov;110(Pt A):480-492 - PubMed
  11. Nat Rev Immunol. 2004 Dec;4(12):931-40 - PubMed
  12. J Immunol. 2014 May 1;192(9):4425-35 - PubMed
  13. J Interferon Cytokine Res. 2004 Feb;24(2):119-29 - PubMed
  14. Nat Protoc. 2012 Mar 01;7(3):562-78 - PubMed
  15. FASEB J. 2010 May;24(5):1479-88 - PubMed
  16. J Neuroimmunol. 1995 Aug;61(1):17-25 - PubMed
  17. Nat Rev Immunol. 2017 Feb;17(2):112-129 - PubMed
  18. J Clin Invest. 2008 May;118(5):1680-90 - PubMed
  19. Crit Rev Clin Lab Sci. 1999 Jun;36(3):165-224 - PubMed
  20. Nature. 2008 Nov 27;456(7221):470-6 - PubMed
  21. J Virol. 2013 Oct;87(20):11244-54 - PubMed
  22. J Biol Chem. 1995 Sep 15;270(37):21606-11 - PubMed
  23. J Med Microbiol. 2007 Sep;56(Pt 9):1230-1234 - PubMed
  24. Bioinformatics. 2002 Jan;18(1):207-8 - PubMed
  25. Appl Environ Microbiol. 1985 Jul;50(1):91-3 - PubMed
  26. FASEB J. 1991 Aug;5(11):2567-74 - PubMed
  27. Br J Clin Pharmacol. 2016 Jul;82(1):64-73 - PubMed
  28. Cell Mol Immunol. 2015 Sep;12(5):633-44 - PubMed
  29. Sci Rep. 2017 Nov 29;7(1):16585 - PubMed
  30. Nat Rev Immunol. 2005 May;5(5):375-86 - PubMed
  31. Clin Chim Acta. 2002 Sep;323(1-2):59-72 - PubMed
  32. J Biol Chem. 1992 Feb 5;267(4):2802-9 - PubMed
  33. J Immunol Methods. 2009 Dec 31;351(1-2):41-5 - PubMed
  34. Mol Immunol. 2018 Jan;93:20-30 - PubMed
  35. J Biol Chem. 1995 Jul 7;270(27):15974-8 - PubMed
  36. J Leukoc Biol. 1995 May;57(5):712-8 - PubMed
  37. Leukemia. 2018 May;32(5):1081-1093 - PubMed
  38. FEBS Lett. 1992 Dec 21;314(3):445-8 - PubMed
  39. Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19689-94 - PubMed
  40. Neuroscience. 2015 Aug 27;302:2-22 - PubMed
  41. Cell. 1994 May 6;77(3):391-400 - PubMed
  42. Cell. 1995 May 19;81(4):551-60 - PubMed
  43. Int Rev Cell Mol Biol. 2016;326:343-72 - PubMed
  44. Anal Biochem. 1987 Apr;162(1):156-9 - PubMed
  45. Mult Scler. 2017 Jun;23(7):937-945 - PubMed
  46. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6138-43 - PubMed

Publication Types

Grant support