Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation.
IFNAR
immunology
interferon
soluble receptors
Journal
Journal of clinical medicine
ISSN: 2077-0383
Titre abrégé: J Clin Med
Pays: Switzerland
ID NLM: 101606588
Informations de publication
Date de publication:
31 Mar 2020
31 Mar 2020
Historique:
received:
05
03
2020
revised:
26
03
2020
accepted:
29
03
2020
entrez:
5
4
2020
pubmed:
5
4
2020
medline:
5
4
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32244308
pii: jcm9040959
doi: 10.3390/jcm9040959
pmc: PMC7230527
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Instituto de Salud Carlos III
ID : PI13/00927
Organisme : Instituto de Salud Carlos III
ID : DTS/1800045
Organisme : EMBO
ID : Short-Term Fellowships (7902)
Organisme : Consejería de Salud, Junta de Andalucía
ID : EF-0169-2018
Références
J Biol Chem. 2004 Apr 23;279(17):18046-53
pubmed: 14960565
Hum Mol Genet. 2015 Jun 1;24(11):3192-205
pubmed: 25721402
PLoS One. 2015 Mar 26;10(3):e0122672
pubmed: 25811193
Expert Opin Investig Drugs. 2000 Mar;9(3):497-514
pubmed: 11060691
PLoS One. 2014 Dec 05;9(12):e113840
pubmed: 25478795
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Blood. 2001 Jan 15;97(2):473-82
pubmed: 11154225
Bioanalysis. 2015;7(22):2869-80
pubmed: 26571364
BMC Genomics. 2015 Jan 23;16:26
pubmed: 25613284
Neuropharmacology. 2016 Nov;110(Pt A):480-492
pubmed: 27452720
Nat Rev Immunol. 2004 Dec;4(12):931-40
pubmed: 15573128
J Immunol. 2014 May 1;192(9):4425-35
pubmed: 24696235
J Interferon Cytokine Res. 2004 Feb;24(2):119-29
pubmed: 14980076
Nat Protoc. 2012 Mar 01;7(3):562-78
pubmed: 22383036
FASEB J. 2010 May;24(5):1479-88
pubmed: 20019241
J Neuroimmunol. 1995 Aug;61(1):17-25
pubmed: 7560008
Nat Rev Immunol. 2017 Feb;17(2):112-129
pubmed: 28028310
J Clin Invest. 2008 May;118(5):1680-90
pubmed: 18382764
Crit Rev Clin Lab Sci. 1999 Jun;36(3):165-224
pubmed: 10407682
Nature. 2008 Nov 27;456(7221):470-6
pubmed: 18978772
J Virol. 2013 Oct;87(20):11244-54
pubmed: 23946454
J Biol Chem. 1995 Sep 15;270(37):21606-11
pubmed: 7665574
J Med Microbiol. 2007 Sep;56(Pt 9):1230-1234
pubmed: 17761488
Bioinformatics. 2002 Jan;18(1):207-8
pubmed: 11836235
Appl Environ Microbiol. 1985 Jul;50(1):91-3
pubmed: 3896144
FASEB J. 1991 Aug;5(11):2567-74
pubmed: 1868981
Br J Clin Pharmacol. 2016 Jul;82(1):64-73
pubmed: 26972584
Cell Mol Immunol. 2015 Sep;12(5):633-44
pubmed: 25176527
Sci Rep. 2017 Nov 29;7(1):16585
pubmed: 29185487
Nat Rev Immunol. 2005 May;5(5):375-86
pubmed: 15864272
Clin Chim Acta. 2002 Sep;323(1-2):59-72
pubmed: 12135807
J Biol Chem. 1992 Feb 5;267(4):2802-9
pubmed: 1370833
J Immunol Methods. 2009 Dec 31;351(1-2):41-5
pubmed: 19786034
Mol Immunol. 2018 Jan;93:20-30
pubmed: 29127843
J Biol Chem. 1995 Jul 7;270(27):15974-8
pubmed: 7608155
J Leukoc Biol. 1995 May;57(5):712-8
pubmed: 7759950
Leukemia. 2018 May;32(5):1081-1093
pubmed: 29467484
FEBS Lett. 1992 Dec 21;314(3):445-8
pubmed: 1468582
Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19689-94
pubmed: 22106296
Neuroscience. 2015 Aug 27;302:2-22
pubmed: 26117714
Cell. 1994 May 6;77(3):391-400
pubmed: 8181059
Cell. 1995 May 19;81(4):551-60
pubmed: 7758109
Int Rev Cell Mol Biol. 2016;326:343-72
pubmed: 27572132
Anal Biochem. 1987 Apr;162(1):156-9
pubmed: 2440339
Mult Scler. 2017 Jun;23(7):937-945
pubmed: 27613121
Proc Natl Acad Sci U S A. 2001 May 22;98(11):6138-43
pubmed: 11344274