Screening and characterization of molecules that modulate the biological activity of IFNs-I.

2.50
Hdl Handle:
http://hdl.handle.net/10033/618730
Title:
Screening and characterization of molecules that modulate the biological activity of IFNs-I.
Authors:
Bürgi, Milagros; Zapol'skii, Viktor A; Hinkelmann, Bettina; Köster, Mario; Kaufmann, Dieter E; Sasse, Florenz; Hauser, Hansjörg; Etcheverrigaray, Marina; Kratje, Ricardo; Bollati-Fogolín, Mariela ( 0000-0001-6829-3135 ) ; Oggero, Marcos
Abstract:
Type I Interferons (IFNs-I) are species-specific glycoproteins which play an important role as primary defence against viral infections and that can also modulate the adaptive immune system. In some autoimmune diseases, interferons (IFNs) are over-produced. IFNs are widely used as biopharmaceuticals for a variety of cancer indications, chronic viral diseases, and for their immuno-modulatory action in patients with multiple sclerosis; therefore, increasing their therapeutic efficiency and decreasing their side effects is of high clinical value. In this sense, it is interesting to find molecules that can modulate the activity of IFNs. In order to achieve that, it was necessary to establish a simple, fast and robust assay to analyze numerous compounds simultaneously. We developed four reporter gene assays (RGAs) to identify IFN activity modulator compounds by using WISH-Mx2/EGFP, HeLa-Mx2/EGFP, A549-Mx2/EGFP, and HEp2-Mx2/EGFP reporter cell lines (RCLs). All of them present a Z' factor higher than 0.7. By using these RGAs, natural and synthetic compounds were analyzed simultaneously. A total of 442 compounds were studied by the Low Throughput Screening (LTS) assay using the four RCLs to discriminate between their inhibitory or enhancing effects on IFN activity. Some of them were characterized and 15 leads were identified. Finally, one promising candidate with enhancing effect on IFN-α/-β activity and five compounds with inhibitory effect were described.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7,38124 Braunschweig, Germany.
Citation:
Screening and characterization of molecules that modulate the biological activity of IFNs-I. 2016, 233:6-16 J. Biotechnol.
Journal:
Journal of biotechnology
Issue Date:
10-Sep-2016
URI:
http://hdl.handle.net/10033/618730
DOI:
10.1016/j.jbiotec.2016.06.021
PubMed ID:
27346232
Type:
Article
Language:
en
ISSN:
1873-4863
Appears in Collections:
Publications of the research group Chemical Biology (CBIO)

Full metadata record

DC FieldValue Language
dc.contributor.authorBürgi, Milagrosen
dc.contributor.authorZapol'skii, Viktor Aen
dc.contributor.authorHinkelmann, Bettinaen
dc.contributor.authorKöster, Marioen
dc.contributor.authorKaufmann, Dieter Een
dc.contributor.authorSasse, Florenzen
dc.contributor.authorHauser, Hansjörgen
dc.contributor.authorEtcheverrigaray, Marinaen
dc.contributor.authorKratje, Ricardoen
dc.contributor.authorBollati-Fogolín, Marielaen
dc.contributor.authorOggero, Marcosen
dc.date.accessioned2016-08-24T11:08:33Z-
dc.date.available2016-08-24T11:08:33Z-
dc.date.issued2016-09-10-
dc.identifier.citationScreening and characterization of molecules that modulate the biological activity of IFNs-I. 2016, 233:6-16 J. Biotechnol.en
dc.identifier.issn1873-4863-
dc.identifier.pmid27346232-
dc.identifier.doi10.1016/j.jbiotec.2016.06.021-
dc.identifier.urihttp://hdl.handle.net/10033/618730-
dc.description.abstractType I Interferons (IFNs-I) are species-specific glycoproteins which play an important role as primary defence against viral infections and that can also modulate the adaptive immune system. In some autoimmune diseases, interferons (IFNs) are over-produced. IFNs are widely used as biopharmaceuticals for a variety of cancer indications, chronic viral diseases, and for their immuno-modulatory action in patients with multiple sclerosis; therefore, increasing their therapeutic efficiency and decreasing their side effects is of high clinical value. In this sense, it is interesting to find molecules that can modulate the activity of IFNs. In order to achieve that, it was necessary to establish a simple, fast and robust assay to analyze numerous compounds simultaneously. We developed four reporter gene assays (RGAs) to identify IFN activity modulator compounds by using WISH-Mx2/EGFP, HeLa-Mx2/EGFP, A549-Mx2/EGFP, and HEp2-Mx2/EGFP reporter cell lines (RCLs). All of them present a Z' factor higher than 0.7. By using these RGAs, natural and synthetic compounds were analyzed simultaneously. A total of 442 compounds were studied by the Low Throughput Screening (LTS) assay using the four RCLs to discriminate between their inhibitory or enhancing effects on IFN activity. Some of them were characterized and 15 leads were identified. Finally, one promising candidate with enhancing effect on IFN-α/-β activity and five compounds with inhibitory effect were described.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-sa/4.0/*
dc.titleScreening and characterization of molecules that modulate the biological activity of IFNs-I.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7,38124 Braunschweig, Germany.en
dc.identifier.journalJournal of biotechnologyen

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