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 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 ne

SUBMITTER: Boonmee A 

PROVIDER: S-EPMC8566489 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature