Dimethyl itaconate is not metabolized into itaconate intracellularly [Immunology]

Itaconic acid is an important metabolite produced by macrophages after stimulation with LPS. The role of itaconate in the inflammatory cascade is unclear. Here we used 13C-itaconate and 13C-dimethyl itaconate (DMI) to probe itaconate metabolism, and find that 13C-DMI is not metabolized to itaconate. 13C-itaconate in the cell culture medium leads to elevated intracellular levels of unlabeled succinate, with no evidence of intracellular uptake. The goal of this report is to encourage the development effective pro-drug strategies to increase the intracellular levels of itaconate, which will enable more conclusive analysis of its action on macrophages and other cell and tissue types.

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