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- W4313374505 abstract "Abstract Following the discovery of itaconate’s immunoregulatory properties, several ester derivatives of this dicarboxylic acid were designed to further examine its role. Here, we compare the metabolic, electrophilic, and immunologic profiles of macrophages treated with unmodified itaconate and a panel of itaconate derivatives. Using WT and Irg1-deficient macrophages, we show that neither dimethyl itaconate (DI) nor 4-octyl itaconate (4OI) are converted into intracellular itaconate in either resting or TLR-activated cells, 4-monoethyl itaconate (4EI) yields only small quantities of intracellular itaconate, while exogenous itaconic acid readily enters macrophages and accumulates to physiologically relevant amounts. We find that both DI and 4OI induce a strong electrophilic stress response, in contrast to itaconate and 4EI. This correlated with their differential immunological impact: DI and 4OI both inhibited IκBζ induction and IL-6 secretion. In contrast, itaconate treatment had minimal impact on IκBζ, IL-6 and pro-IL-1β levels, but demonstrated a distinct defect in IL-1β secretion. Altogether, this systematic evaluation stresses the importance of using unmodified itaconate in future mechanistic studies." @default.
- W4313374505 created "2023-01-06" @default.
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- W4313374505 date "2020-05-01" @default.
- W4313374505 modified "2023-10-16" @default.
- W4313374505 title "Comparative evaluation of metabolic, electrophilic, and immunologic effects of itaconate and its ester derivatives on macrophage activation" @default.
- W4313374505 doi "https://doi.org/10.4049/jimmunol.204.supp.73.1" @default.
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