Swain, Amanda published the artcileComparative evaluation of itaconate and its derivatives reveals divergent inflammasome and type I interferon regulation in macrophages, Application In Synthesis of 617-52-7, the publication is Nature Metabolism (2020), 2(7), 594-602, database is CAplus and MEDLINE.
Following activation, macrophages undergo extensive metabolic rewiring1,2. Production of itaconate through the inducible enzyme IRG1 is a key hallmark of this process3. Itaconate inhibits succinate dehydrogenase4,5, has electrophilic properties6 and is associated with a change in cytokine production4. Here, we compare the metabolic, electrophilic and immunol. profiles of macrophages treated with unmodified itaconate and a panel of commonly used itaconate derivatives to examine its role. Using wild-type and Irg1-/- macrophages, we show that neither di-Me itaconate, 4-octyl itaconate nor 4-monoethyl itaconate are converted to intracellular itaconate, while exogenous itaconic acid readily enters macrophages. We find that only di-Me itaconate and 4-octyl itaconate induce a strong electrophilic stress response, in contrast to itaconate and 4-monoethyl itaconate. This correlates with their immunosuppressive phenotype: di-Me itaconate and 4-octyl itaconate inhibited IκBζ and pro-interleukin (IL)-1β induction, as well as IL-6, IL-10 and interferon-β secretion, in an NRF2-independent manner. In contrast, itaconate treatment suppressed IL-1β secretion but not pro-IL-1β levels and, surprisingly, strongly enhanced lipopolysaccharide-induced interferon-β secretion. Consistently, Irg1-/- macrophages produced lower levels of interferon and reduced transcriptional activation of this pathway. Our work establishes itaconate as an immunoregulatory, rather than strictly immunosuppressive, metabolite and highlights the importance of using unmodified itaconate in future studies.
Nature Metabolism published new progress about 617-52-7. 617-52-7 belongs to esters-buliding-blocks, auxiliary class Alkenyl,Aliphatic hydrocarbon chain,Ester, name is Dimethyl itaconate, and the molecular formula is C7H8BClO2, Application In Synthesis of 617-52-7.
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https://en.wikipedia.org/wiki/Ester,
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