The BET inhibitor attenuates the inflammatory response and cell migration in human microglial HMC3 cell line

Abstract Microglia, resident macrophages of the brain that act as primary immune cells, play essential roles in innate immunity and neuroinflammatory pathologies. Microglial cells are rapidly activated in response to infection and inflammation/injury, associated with the expression of proinflammator...

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Autores principales:	Mina Baek, Eunyoung Yoo, Hae In Choi, Ga Yeong An, Jin Choul Chai, Young Seek Lee, Kyoung Hwa Jung, Young Gyu Chai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7a8daae75c6342daab790352521888f4
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spelling	oai:doaj.org-article:7a8daae75c6342daab790352521888f42021-12-02T17:32:59ZThe BET inhibitor attenuates the inflammatory response and cell migration in human microglial HMC3 cell line10.1038/s41598-021-87828-12045-2322https://doaj.org/article/7a8daae75c6342daab790352521888f42021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87828-1https://doaj.org/toc/2045-2322Abstract Microglia, resident macrophages of the brain that act as primary immune cells, play essential roles in innate immunity and neuroinflammatory pathologies. Microglial cells are rapidly activated in response to infection and inflammation/injury, associated with the expression of proinflammatory genes and secretion of cytokines. The bromodomain and extra-terminal (BET) inhibitor JQ1 has been shown to be an epigenetic agent that reduces inflammation. In this study, we investigated the mechanisms underlying the anti-inflammatory and anti-migratory functions of JQ1 and the genes targeted by JQ1 in lipopolysaccharide (LPS)-activated human microglial clone 3 (HMC3) cells using RNA-sequencing (RNA-seq). We analyzed the pattern of inflammation-related genes (chemokines, cytokines, and interferon-stimulated genes) and migration-related genes with JQ1 treatment from differentially expressed genes analysis in HMC3 cells. We found that LPS-induced IRF1 directly regulated inflammation- and migration-related genes and that JQ1 significantly reduced IRF1 and its target genes. Additionally, IRF1 attenuation significantly downregulated target genes and inhibited microglial migration. Our data suggest that the BET inhibitor JQ1 can modulate the inflammatory response and migration through the regulation of LPS-induced IRF1 in human microglia.Mina BaekEunyoung YooHae In ChoiGa Yeong AnJin Choul ChaiYoung Seek LeeKyoung Hwa JungYoung Gyu ChaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mina Baek Eunyoung Yoo Hae In Choi Ga Yeong An Jin Choul Chai Young Seek Lee Kyoung Hwa Jung Young Gyu Chai The BET inhibitor attenuates the inflammatory response and cell migration in human microglial HMC3 cell line
description	Abstract Microglia, resident macrophages of the brain that act as primary immune cells, play essential roles in innate immunity and neuroinflammatory pathologies. Microglial cells are rapidly activated in response to infection and inflammation/injury, associated with the expression of proinflammatory genes and secretion of cytokines. The bromodomain and extra-terminal (BET) inhibitor JQ1 has been shown to be an epigenetic agent that reduces inflammation. In this study, we investigated the mechanisms underlying the anti-inflammatory and anti-migratory functions of JQ1 and the genes targeted by JQ1 in lipopolysaccharide (LPS)-activated human microglial clone 3 (HMC3) cells using RNA-sequencing (RNA-seq). We analyzed the pattern of inflammation-related genes (chemokines, cytokines, and interferon-stimulated genes) and migration-related genes with JQ1 treatment from differentially expressed genes analysis in HMC3 cells. We found that LPS-induced IRF1 directly regulated inflammation- and migration-related genes and that JQ1 significantly reduced IRF1 and its target genes. Additionally, IRF1 attenuation significantly downregulated target genes and inhibited microglial migration. Our data suggest that the BET inhibitor JQ1 can modulate the inflammatory response and migration through the regulation of LPS-induced IRF1 in human microglia.
format	article
author	Mina Baek Eunyoung Yoo Hae In Choi Ga Yeong An Jin Choul Chai Young Seek Lee Kyoung Hwa Jung Young Gyu Chai
author_facet	Mina Baek Eunyoung Yoo Hae In Choi Ga Yeong An Jin Choul Chai Young Seek Lee Kyoung Hwa Jung Young Gyu Chai
author_sort	Mina Baek
title	The BET inhibitor attenuates the inflammatory response and cell migration in human microglial HMC3 cell line
title_short	The BET inhibitor attenuates the inflammatory response and cell migration in human microglial HMC3 cell line
title_full	The BET inhibitor attenuates the inflammatory response and cell migration in human microglial HMC3 cell line
title_fullStr	The BET inhibitor attenuates the inflammatory response and cell migration in human microglial HMC3 cell line
title_full_unstemmed	The BET inhibitor attenuates the inflammatory response and cell migration in human microglial HMC3 cell line
title_sort	bet inhibitor attenuates the inflammatory response and cell migration in human microglial hmc3 cell line
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7a8daae75c6342daab790352521888f4
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The BET inhibitor attenuates the inflammatory response and cell migration in human microglial HMC3 cell line

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