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1.
J Clin Med ; 9(4)2020 Mar 31.
Article in English | MEDLINE | ID: mdl-32244308

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-É£ 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.

2.
Bioanalysis ; 7(22): 2869-80, 2015.
Article in English | MEDLINE | ID: mdl-26571364

ABSTRACT

AIM: The soluble isoform of the IFN-ß receptor (sIFNAR2) can bind IFN-ß and modulate its activity, although its role in autoimmune diseases remains unknown. METHODS: A recombinant human sIFNAR2 protein was cloned, expressed and purified after which we developed and validated an ELISA for its quantification in human serum. Serum sIFNAR2 were assessed in multiple sclerosis (MS) patients and healthy controls. RESULTS: The ELISA has a dynamic range of 3.9-250 ng/ml and a detection limit of 2.44 ng/ml. Serum sIFNAR2 were significantly lower in untreated-MS patients than in healthy controls. CONCLUSION: The ELISA is suitable for quantification of sIFNAR2 in serum and should facilitate the study of sIFNAR2 in neuroimmunological diseases such as MS.


Subject(s)
Enzyme-Linked Immunosorbent Assay/methods , Multiple Sclerosis/diagnosis , Receptor, Interferon alpha-beta/blood , Recombinant Proteins/metabolism , Case-Control Studies , Humans , Multiple Sclerosis/blood , Reproducibility of Results
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