Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1783369298464473088 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6222831 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT strzadalaleon anantiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT fiedorowiczanna anantiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT wysokinskaedyta anantiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT zioloewa anantiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT grudzienmałgorzata anantiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT jelenmalgorzata anantiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT plutakrystian anantiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT morakmlodawskabeata anantiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT zimeckimichal anantiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT kalaswojciech anantiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT strzadalaleon antiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT fiedorowiczanna antiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT wysokinskaedyta antiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT zioloewa antiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT grudzienmałgorzata antiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT jelenmalgorzata antiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT plutakrystian antiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT morakmlodawskabeata antiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT zimeckimichal antiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells AT kalaswojciech antiinflammatoryazaphenothiazineinhibitsinterferonbexpressionandcxcl10productioninkertrcells |