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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-\u03b1 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-\u03b1), 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, <jats:italic>setdb2, kdm4d<\/jats:italic>, and <jats:italic>suv39h1<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/s41598-021-00955-7","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T11:04:18Z","timestamp":1635937458000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications"],"prefix":"10.1038","volume":"11","author":[{"given":"Atsadang","family":"Boonmee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salisa","family":"Benjaskulluecha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patipark","family":"Kueanjinda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjawan","family":"Wongprom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thitiporn","family":"Pattarakankul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanapat","family":"Palaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,3]]},"reference":[{"key":"955_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093233","volume":"21","author":"K Bukowski","year":"2020","unstructured":"Bukowski, K., Kciuk, M. & Kontek, R. 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