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- W4313430239 abstract "Abstract Choline homeostasis in macrophage biology is important for LPS-polarized inflammation. In macrophages, choline mainly supports phosphatidylcholine (PC) synthesis, which is crucial for membrane production and cytokine secretion. Here, we examined choline metabolism in IL-4 polarized macrophages in vitro and in vivo. Like LPS, IL-4 increased choline transporter-like protein 1 (CTL1) expression, choline uptake and the incorporation of choline into PC. Targeted lipidomics analysis revealed increased PC content in IL-4-polarized macrophages, with an enrichment in low-saturated species. Pharmacological inhibition of choline uptake/choline kinase with hemicholinium-3 or RSM-932a showed no effect on certain hallmark IL-4-induced macrophage genes (Chil3, Mrc1, Arg1) but significantly reduced the transcript and protein expression of RELMα. Consistent with the function of RELMα in wound healing, 3T3-L1 cells healed more slowly in a scratch wound assay with conditioned media from IL-4 polarized macrophages in which choline metabolism was inhibited compared to vehicle-treated conditioned media. In addition, inhibiting choline metabolism completely prevented PD-L2 upregulation and increased PD-L1 expression on IL-4-polarized macrophages, together with suppressed cellular respiration and increased glycolysis. Furthermore, in vivo administration of RSM-932a (3 mg/kg i.p.) in C57BL/6J mice lowered RELMα in macrophages, decreased PD-L2 and increased PD-L1, and resulted in a loss of resident peritoneal F4/80hi macrophages. Choline represents an underappreciated regulator of macrophage immunometabolism and strategies to target macrophage choline uptake or choline metabolism may be therapeutically valuable." @default.
- W4313430239 created "2023-01-06" @default.
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- W4313430239 date "2022-05-01" @default.
- W4313430239 modified "2023-09-26" @default.
- W4313430239 title "Choline metabolism underpins macrophage IL-4 polarization <i>in vitro</i> and <i>in vivo</i>" @default.
- W4313430239 doi "https://doi.org/10.4049/jimmunol.208.supp.165.04" @default.
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