The chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications

Abstract Following re-exposure to lipopolysaccharide (LPS), macrophages exhibit an immunosuppressive state known as LPS tolerance, which is characterized by repressed proinflammatory cytokine production. LPS-induced tolerance in macrophages is mediated in part by epigenetic changes. Carboplatin, an...

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Autores principales:	Atsadang Boonmee, Salisa Benjaskulluecha, Patipark Kueanjinda, Benjawan Wongprom, Thitiporn Pattarakankul, Tanapat Palaga
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/938bcade652f4be3b3aee1a5ab3285ca
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spelling	oai:doaj.org-article:938bcade652f4be3b3aee1a5ab3285ca2021-11-08T10:48:42ZThe chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications10.1038/s41598-021-00955-72045-2322https://doaj.org/article/938bcade652f4be3b3aee1a5ab3285ca2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00955-7https://doaj.org/toc/2045-2322Abstract Following re-exposure to lipopolysaccharide (LPS), macrophages exhibit an immunosuppressive state known as LPS tolerance, which is characterized by repressed proinflammatory cytokine production. LPS-induced tolerance in macrophages is mediated in part by epigenetic changes. Carboplatin, an anticancer chemotherapeutic drug, exerts its effect by inhibiting DNA replication and transcription, as well as through epigenetic modifications. Through an unbiased screen, we found that carboplatin rescued TNF-α and IL-6 production in LPS-tolerant macrophages. Transcriptomic analysis and gene set enrichment analyses revealed that p53 was one of the most significantly upregulated hallmarks in both LPS-primed and LPS-tolerant macrophages in the presence of carboplatin, while E2F and G2/M were the most negatively regulated hallmarks. Heterochromatin protein 1 (HP1-α), which is associated with gene silencing, was significantly reduced in carboplatin-treated LPS-tolerant macrophages at the mRNA and protein levels. Dynamic changes in the mRNA level of genes encoding H3K9me3 methyltransferases, setdb2, kdm4d, and suv39h1 were induced in the presence of carboplatin in LPS-tolerant macrophages. Taken together, we provide evidence that carboplatin treatment interferes with proinflammatory cytokine production during the acute LPS response and LPS tolerance in macrophages, possibly via H3K9me3 modification.Atsadang BoonmeeSalisa BenjaskulluechaPatipark KueanjindaBenjawan WongpromThitiporn PattarakankulTanapat PalagaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Atsadang Boonmee Salisa Benjaskulluecha Patipark Kueanjinda Benjawan Wongprom Thitiporn Pattarakankul Tanapat Palaga The chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications
description	Abstract Following re-exposure to lipopolysaccharide (LPS), macrophages exhibit an immunosuppressive state known as LPS tolerance, which is characterized by repressed proinflammatory cytokine production. LPS-induced tolerance in macrophages is mediated in part by epigenetic changes. Carboplatin, an anticancer chemotherapeutic drug, exerts its effect by inhibiting DNA replication and transcription, as well as through epigenetic modifications. Through an unbiased screen, we found that carboplatin rescued TNF-α and IL-6 production in LPS-tolerant macrophages. Transcriptomic analysis and gene set enrichment analyses revealed that p53 was one of the most significantly upregulated hallmarks in both LPS-primed and LPS-tolerant macrophages in the presence of carboplatin, while E2F and G2/M were the most negatively regulated hallmarks. Heterochromatin protein 1 (HP1-α), which is associated with gene silencing, was significantly reduced in carboplatin-treated LPS-tolerant macrophages at the mRNA and protein levels. Dynamic changes in the mRNA level of genes encoding H3K9me3 methyltransferases, setdb2, kdm4d, and suv39h1 were induced in the presence of carboplatin in LPS-tolerant macrophages. Taken together, we provide evidence that carboplatin treatment interferes with proinflammatory cytokine production during the acute LPS response and LPS tolerance in macrophages, possibly via H3K9me3 modification.
format	article
author	Atsadang Boonmee Salisa Benjaskulluecha Patipark Kueanjinda Benjawan Wongprom Thitiporn Pattarakankul Tanapat Palaga
author_facet	Atsadang Boonmee Salisa Benjaskulluecha Patipark Kueanjinda Benjawan Wongprom Thitiporn Pattarakankul Tanapat Palaga
author_sort	Atsadang Boonmee
title	The chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications
title_short	The chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications
title_full	The chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications
title_fullStr	The chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications
title_full_unstemmed	The chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications
title_sort	chemotherapeutic drug carboplatin affects macrophage responses to lps and lps tolerance via epigenetic modifications
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/938bcade652f4be3b3aee1a5ab3285ca
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The chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications

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