RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor

Abstract Persistent microglial activation is associated with the production and secretion of various pro-inflammatory genes, cytokines and chemokines, which may initiate or amplify neurodegenerative diseases. A novel synthetic histone 3 lysine 27 (H3K27) demethylase JMJD3 inhibitor, GSK-J4, was prov...

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Autores principales:	Amitabh Das, Sarder Arifuzzaman, Taeho Yoon, Sun Hwa Kim, Jin Choul Chai, Young Seek Lee, Kyoung Hwa Jung, Young Gyu Chai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f6fc55853b0b4d63a8c8340c456ed953
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spelling	oai:doaj.org-article:f6fc55853b0b4d63a8c8340c456ed9532021-12-02T15:05:34ZRNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor10.1038/s41598-017-06914-52045-2322https://doaj.org/article/f6fc55853b0b4d63a8c8340c456ed9532017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06914-5https://doaj.org/toc/2045-2322Abstract Persistent microglial activation is associated with the production and secretion of various pro-inflammatory genes, cytokines and chemokines, which may initiate or amplify neurodegenerative diseases. A novel synthetic histone 3 lysine 27 (H3K27) demethylase JMJD3 inhibitor, GSK-J4, was proven to exert immunosuppressive activities in macrophages. However, a genome-wide search for GSK-J4 molecular targets has not been undertaken in microglia. To study the immuno-modulatory effects of GSK-J4 at the transcriptomic level, triplicate RNA sequencing and quantitative real-time PCR analyses were performed with resting, GSK-J4-, LPS- and LPS + GSK-J4-challenged primary microglial (PM) and BV-2 microglial cells. Among the annotated genes, the transcriptional sequencing of microglia that were treated with GSK-J4 revealed a selective effect on LPS-induced gene expression, in which the induction of cytokines/chemokines, interferon-stimulated genes, and prominent transcription factors TFs, as well as previously unidentified genes that are important in inflammation was suppressed. Furthermore, we showed that GSK-J4 controls are important inflammatory gene targets by modulating STAT1, IRF7, and H3K27me3 levels at their promoter sites. These unprecedented results demonstrate that the histone demethylase inhibitor GSK-J4 could have therapeutic applications for neuroinflammatory diseases.Amitabh DasSarder ArifuzzamanTaeho YoonSun Hwa KimJin Choul ChaiYoung Seek LeeKyoung Hwa JungYoung Gyu ChaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-19 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amitabh Das Sarder Arifuzzaman Taeho Yoon Sun Hwa Kim Jin Choul Chai Young Seek Lee Kyoung Hwa Jung Young Gyu Chai RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor
description	Abstract Persistent microglial activation is associated with the production and secretion of various pro-inflammatory genes, cytokines and chemokines, which may initiate or amplify neurodegenerative diseases. A novel synthetic histone 3 lysine 27 (H3K27) demethylase JMJD3 inhibitor, GSK-J4, was proven to exert immunosuppressive activities in macrophages. However, a genome-wide search for GSK-J4 molecular targets has not been undertaken in microglia. To study the immuno-modulatory effects of GSK-J4 at the transcriptomic level, triplicate RNA sequencing and quantitative real-time PCR analyses were performed with resting, GSK-J4-, LPS- and LPS + GSK-J4-challenged primary microglial (PM) and BV-2 microglial cells. Among the annotated genes, the transcriptional sequencing of microglia that were treated with GSK-J4 revealed a selective effect on LPS-induced gene expression, in which the induction of cytokines/chemokines, interferon-stimulated genes, and prominent transcription factors TFs, as well as previously unidentified genes that are important in inflammation was suppressed. Furthermore, we showed that GSK-J4 controls are important inflammatory gene targets by modulating STAT1, IRF7, and H3K27me3 levels at their promoter sites. These unprecedented results demonstrate that the histone demethylase inhibitor GSK-J4 could have therapeutic applications for neuroinflammatory diseases.
format	article
author	Amitabh Das Sarder Arifuzzaman Taeho Yoon Sun Hwa Kim Jin Choul Chai Young Seek Lee Kyoung Hwa Jung Young Gyu Chai
author_facet	Amitabh Das Sarder Arifuzzaman Taeho Yoon Sun Hwa Kim Jin Choul Chai Young Seek Lee Kyoung Hwa Jung Young Gyu Chai
author_sort	Amitabh Das
title	RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor
title_short	RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor
title_full	RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor
title_fullStr	RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor
title_full_unstemmed	RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor
title_sort	rna sequencing reveals resistance of tlr4 ligand-activated microglial cells to inflammation mediated by the selective jumonji h3k27 demethylase inhibitor
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f6fc55853b0b4d63a8c8340c456ed953
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RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor

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