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An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells

An azaphenothiazine derivative, 6-chloroethylureidoethyldiquino[3,2-b;2′,3′-e][1,4]thiazine (DQT), has recently been shown to exhibit immunosuppressive activities in mouse models. It also inhibited the expression of CXCL10 at the protein level, at non-toxic concentrations, in the culture of KERTr ce...

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Autores principales: Strzadala, Leon, Fiedorowicz, Anna, Wysokinska, Edyta, Ziolo, Ewa, Grudzień, Małgorzata, Jelen, Malgorzata, Pluta, Krystian, Morak-Mlodawska, Beata, Zimecki, Michal, Kalas, Wojciech
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222831/
https://www.ncbi.nlm.nih.gov/pubmed/30250011
http://dx.doi.org/10.3390/molecules23102443
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author Strzadala, Leon
Fiedorowicz, Anna
Wysokinska, Edyta
Ziolo, Ewa
Grudzień, Małgorzata
Jelen, Malgorzata
Pluta, Krystian
Morak-Mlodawska, Beata
Zimecki, Michal
Kalas, Wojciech
author_facet Strzadala, Leon
Fiedorowicz, Anna
Wysokinska, Edyta
Ziolo, Ewa
Grudzień, Małgorzata
Jelen, Malgorzata
Pluta, Krystian
Morak-Mlodawska, Beata
Zimecki, Michal
Kalas, Wojciech
author_sort Strzadala, Leon
collection PubMed
description An azaphenothiazine derivative, 6-chloroethylureidoethyldiquino[3,2-b;2′,3′-e][1,4]thiazine (DQT), has recently been shown to exhibit immunosuppressive activities in mouse models. It also inhibited the expression of CXCL10 at the protein level, at non-toxic concentrations, in the culture of KERTr cells treated with double-stranded RNA, poly(I:C). In this report, we demonstrated that DQT inhibits the transcription of the CXCL10 gene. Although CXCL10 is an IFNγ-inducible protein, we found that the CXCL10 protein was induced without the detectable release of IFNγ or IκB degradation. Hence, we concluded that IFNγ or NFκB was not involved in the regulation of the CXCL10 gene in KERTr cells transfected with poly(I:C), nor in the inhibitory activity of DQT. On the other hand, we found that IFNβ was induced under the same conditions and that its expression was inhibited by DQT. Kinetic analysis showed that an increase in IFNβ concentrations occurred 4–8 h after poly(I:C) treatment, while the concentration of CXCL10 was undetectable at that time and started to increase later, when IFNβ reached high levels. Therefore, DQT may be regarded as a new promising inhibitor of IFNβ expression and IFNβ-dependent downstream genes and proteins, e.g., CXCL10 chemokine, which is implicated in the pathogenesis of autoimmune diseases.
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spelling pubmed-62228312018-11-13 An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells Strzadala, Leon Fiedorowicz, Anna Wysokinska, Edyta Ziolo, Ewa Grudzień, Małgorzata Jelen, Malgorzata Pluta, Krystian Morak-Mlodawska, Beata Zimecki, Michal Kalas, Wojciech Molecules Communication An azaphenothiazine derivative, 6-chloroethylureidoethyldiquino[3,2-b;2′,3′-e][1,4]thiazine (DQT), has recently been shown to exhibit immunosuppressive activities in mouse models. It also inhibited the expression of CXCL10 at the protein level, at non-toxic concentrations, in the culture of KERTr cells treated with double-stranded RNA, poly(I:C). In this report, we demonstrated that DQT inhibits the transcription of the CXCL10 gene. Although CXCL10 is an IFNγ-inducible protein, we found that the CXCL10 protein was induced without the detectable release of IFNγ or IκB degradation. Hence, we concluded that IFNγ or NFκB was not involved in the regulation of the CXCL10 gene in KERTr cells transfected with poly(I:C), nor in the inhibitory activity of DQT. On the other hand, we found that IFNβ was induced under the same conditions and that its expression was inhibited by DQT. Kinetic analysis showed that an increase in IFNβ concentrations occurred 4–8 h after poly(I:C) treatment, while the concentration of CXCL10 was undetectable at that time and started to increase later, when IFNβ reached high levels. Therefore, DQT may be regarded as a new promising inhibitor of IFNβ expression and IFNβ-dependent downstream genes and proteins, e.g., CXCL10 chemokine, which is implicated in the pathogenesis of autoimmune diseases. MDPI 2018-09-24 /pmc/articles/PMC6222831/ /pubmed/30250011 http://dx.doi.org/10.3390/molecules23102443 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Strzadala, Leon
Fiedorowicz, Anna
Wysokinska, Edyta
Ziolo, Ewa
Grudzień, Małgorzata
Jelen, Malgorzata
Pluta, Krystian
Morak-Mlodawska, Beata
Zimecki, Michal
Kalas, Wojciech
An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells
title An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells
title_full An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells
title_fullStr An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells
title_full_unstemmed An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells
title_short An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells
title_sort anti-inflammatory azaphenothiazine inhibits interferon β expression and cxcl10 production in kertr cells
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222831/
https://www.ncbi.nlm.nih.gov/pubmed/30250011
http://dx.doi.org/10.3390/molecules23102443
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