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Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening
Dendritic cells (DCs) play a critical role in the pathogenesis of autoimmune diseases including multiple sclerosis, and targeting DCs’ cytokines production is an important strategy for autoimmune diseases treatment. By establishing a high-throughput screening system, we analyzed LOPAC drug library t...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341058/ https://www.ncbi.nlm.nih.gov/pubmed/28272439 http://dx.doi.org/10.1038/srep43820 |
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author | Chen, Shuai Zhou, Jinfeng Cai, Yingying Zheng, Xinyuan Xie, Sirong Liao, Yuhan Zhu, Yu Qin, Chaoyan Lai, Weiming Yang, Cuixia Xie, Xin Du, Changsheng |
author_facet | Chen, Shuai Zhou, Jinfeng Cai, Yingying Zheng, Xinyuan Xie, Sirong Liao, Yuhan Zhu, Yu Qin, Chaoyan Lai, Weiming Yang, Cuixia Xie, Xin Du, Changsheng |
author_sort | Chen, Shuai |
collection | PubMed |
description | Dendritic cells (DCs) play a critical role in the pathogenesis of autoimmune diseases including multiple sclerosis, and targeting DCs’ cytokines production is an important strategy for autoimmune diseases treatment. By establishing a high-throughput screening system, we analyzed LOPAC drug library to identify drugs that control the secretion of IL-6 by DCs, we selected the most likely candidate drug, BVDU, and found that it affected not only IL-6 production, but also that of IL-12, IL-1β during the DCs differentiation and maturation. The mechanism studies showed that BVDU treatment restricted the phosphorylation of MAP kinase, which played an important role in DC cytokine production. We further assessed the in vivo therapeutic potentials of BVDU on mouse models including EAE and STZ-induced T1D, and found that BVDU treated EAE mice exhibited significantly lower EAE clinical scores, decreased leukocyte infiltration in central nervous system lesions, and reduced demyelination. As in T1D mice, BVDU treatment also showed promising therapeutic effects based on both alleviated disease symptoms and tissue pathogenesis. More interestingly, the modulating effect of BVDU on IL-6 production was further verified in human primary DCs. The above data supported the promising application of our screen model, and also the potential of BVDU for autoimmune diseases therapy. |
format | Online Article Text |
id | pubmed-5341058 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53410582017-03-10 Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening Chen, Shuai Zhou, Jinfeng Cai, Yingying Zheng, Xinyuan Xie, Sirong Liao, Yuhan Zhu, Yu Qin, Chaoyan Lai, Weiming Yang, Cuixia Xie, Xin Du, Changsheng Sci Rep Article Dendritic cells (DCs) play a critical role in the pathogenesis of autoimmune diseases including multiple sclerosis, and targeting DCs’ cytokines production is an important strategy for autoimmune diseases treatment. By establishing a high-throughput screening system, we analyzed LOPAC drug library to identify drugs that control the secretion of IL-6 by DCs, we selected the most likely candidate drug, BVDU, and found that it affected not only IL-6 production, but also that of IL-12, IL-1β during the DCs differentiation and maturation. The mechanism studies showed that BVDU treatment restricted the phosphorylation of MAP kinase, which played an important role in DC cytokine production. We further assessed the in vivo therapeutic potentials of BVDU on mouse models including EAE and STZ-induced T1D, and found that BVDU treated EAE mice exhibited significantly lower EAE clinical scores, decreased leukocyte infiltration in central nervous system lesions, and reduced demyelination. As in T1D mice, BVDU treatment also showed promising therapeutic effects based on both alleviated disease symptoms and tissue pathogenesis. More interestingly, the modulating effect of BVDU on IL-6 production was further verified in human primary DCs. The above data supported the promising application of our screen model, and also the potential of BVDU for autoimmune diseases therapy. Nature Publishing Group 2017-03-08 /pmc/articles/PMC5341058/ /pubmed/28272439 http://dx.doi.org/10.1038/srep43820 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Chen, Shuai Zhou, Jinfeng Cai, Yingying Zheng, Xinyuan Xie, Sirong Liao, Yuhan Zhu, Yu Qin, Chaoyan Lai, Weiming Yang, Cuixia Xie, Xin Du, Changsheng Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening |
title | Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening |
title_full | Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening |
title_fullStr | Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening |
title_full_unstemmed | Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening |
title_short | Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening |
title_sort | discovery of bvdu as a promising drug for autoimmune diseases therapy by dendritic-cell-based functional screening |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341058/ https://www.ncbi.nlm.nih.gov/pubmed/28272439 http://dx.doi.org/10.1038/srep43820 |
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