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IRF5 is elevated in childhood-onset SLE and regulated by histone acetyltransferase and histone deacetylase inhibitors

Interferon regulatory factor 5 (IRF5) plays a critical role in the induction of type I interferon, proinflammatory cytokines and chemokines, and participates in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). However, the relationship between IRF5 and childhood-on...

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Autores principales: Shu, Jin, Li, Ling, Zhou, Lan-Bo, Qian, Jun, Fan, Zhi-Dan, Zhuang, Li-Li, Wang, Lu-Lu, Jin, Rui, Yu, Hai-Guo, Zhou, Guo-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564555/
https://www.ncbi.nlm.nih.gov/pubmed/28525378
http://dx.doi.org/10.18632/oncotarget.17586
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author Shu, Jin
Li, Ling
Zhou, Lan-Bo
Qian, Jun
Fan, Zhi-Dan
Zhuang, Li-Li
Wang, Lu-Lu
Jin, Rui
Yu, Hai-Guo
Zhou, Guo-Ping
author_facet Shu, Jin
Li, Ling
Zhou, Lan-Bo
Qian, Jun
Fan, Zhi-Dan
Zhuang, Li-Li
Wang, Lu-Lu
Jin, Rui
Yu, Hai-Guo
Zhou, Guo-Ping
author_sort Shu, Jin
collection PubMed
description Interferon regulatory factor 5 (IRF5) plays a critical role in the induction of type I interferon, proinflammatory cytokines and chemokines, and participates in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). However, the relationship between IRF5 and childhood-onset SLE remains elusive. In the present study, we demonstrated that levels of mRNA expression of IRF5, IFN-α, and Sp1 were significantly increased in childhood-onset SLE, as seen on quantitative real-time PCR, and the expression of Sp1 and IFN-α was positively correlated with IRF5. In addition to being used as antitumor drugs, a number of histone deacetylase inhibitors (HDACi) display potent anti-inflammatory properties; however, their effects on IRF5 expression remain unclear. In this study, we identified that HDACi trichostatin A (TSA) and histone acetyltransferase (HAT)-p300 downregulated IRF5 promoter activity, mRNA expression, and protein level, whereas the HAT-p300/CBP-associated factor had no effect. Moreover, TSA inhibited the production of TNF-α and IL-6 in differentiated THP-1cells. Furthermore, chromatin immunoprecipitation assays revealed that TSA inhibited DNA binding of Sp1, RNA polymerase II, HDAC3, and p300 to the core promoter region of IRF5. Our results suggest that HDACi may have therapeutic potential in patients with autoimmune diseases such as SLE through repression of IRF5 expression.
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spelling pubmed-55645552017-08-23 IRF5 is elevated in childhood-onset SLE and regulated by histone acetyltransferase and histone deacetylase inhibitors Shu, Jin Li, Ling Zhou, Lan-Bo Qian, Jun Fan, Zhi-Dan Zhuang, Li-Li Wang, Lu-Lu Jin, Rui Yu, Hai-Guo Zhou, Guo-Ping Oncotarget Research Paper Interferon regulatory factor 5 (IRF5) plays a critical role in the induction of type I interferon, proinflammatory cytokines and chemokines, and participates in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). However, the relationship between IRF5 and childhood-onset SLE remains elusive. In the present study, we demonstrated that levels of mRNA expression of IRF5, IFN-α, and Sp1 were significantly increased in childhood-onset SLE, as seen on quantitative real-time PCR, and the expression of Sp1 and IFN-α was positively correlated with IRF5. In addition to being used as antitumor drugs, a number of histone deacetylase inhibitors (HDACi) display potent anti-inflammatory properties; however, their effects on IRF5 expression remain unclear. In this study, we identified that HDACi trichostatin A (TSA) and histone acetyltransferase (HAT)-p300 downregulated IRF5 promoter activity, mRNA expression, and protein level, whereas the HAT-p300/CBP-associated factor had no effect. Moreover, TSA inhibited the production of TNF-α and IL-6 in differentiated THP-1cells. Furthermore, chromatin immunoprecipitation assays revealed that TSA inhibited DNA binding of Sp1, RNA polymerase II, HDAC3, and p300 to the core promoter region of IRF5. Our results suggest that HDACi may have therapeutic potential in patients with autoimmune diseases such as SLE through repression of IRF5 expression. Impact Journals LLC 2017-05-03 /pmc/articles/PMC5564555/ /pubmed/28525378 http://dx.doi.org/10.18632/oncotarget.17586 Text en Copyright: © 2017 Shu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Shu, Jin
Li, Ling
Zhou, Lan-Bo
Qian, Jun
Fan, Zhi-Dan
Zhuang, Li-Li
Wang, Lu-Lu
Jin, Rui
Yu, Hai-Guo
Zhou, Guo-Ping
IRF5 is elevated in childhood-onset SLE and regulated by histone acetyltransferase and histone deacetylase inhibitors
title IRF5 is elevated in childhood-onset SLE and regulated by histone acetyltransferase and histone deacetylase inhibitors
title_full IRF5 is elevated in childhood-onset SLE and regulated by histone acetyltransferase and histone deacetylase inhibitors
title_fullStr IRF5 is elevated in childhood-onset SLE and regulated by histone acetyltransferase and histone deacetylase inhibitors
title_full_unstemmed IRF5 is elevated in childhood-onset SLE and regulated by histone acetyltransferase and histone deacetylase inhibitors
title_short IRF5 is elevated in childhood-onset SLE and regulated by histone acetyltransferase and histone deacetylase inhibitors
title_sort irf5 is elevated in childhood-onset sle and regulated by histone acetyltransferase and histone deacetylase inhibitors
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564555/
https://www.ncbi.nlm.nih.gov/pubmed/28525378
http://dx.doi.org/10.18632/oncotarget.17586
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