Home > Publications Database > Mesaconate is synthesized from itaconate and exerts immunomodulatory effects in macrophages. > print

001     164641
005     20240110092047.0
024 7 _ |a pmc:PMC9744384
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024 7 _ |a 10.1038/s42255-022-00565-1
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024 7 _ |a pmid:35655024
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037 _ _ |a DZNE-2022-01171
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a He, Wei
|b 0
245 _ _ |a Mesaconate is synthesized from itaconate and exerts immunomodulatory effects in macrophages.
260 _ _ |a [London]
|c 2022
|b Springer Nature
336 7 _ |a article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Since its discovery in inflammatory macrophages, itaconate has attracted much attention due to its antimicrobial and immunomodulatory activity1-3. However, instead of investigating itaconate itself, most studies used derivatized forms of itaconate and thus the role of non-derivatized itaconate needs to be scrutinized. Mesaconate, a metabolite structurally very close to itaconate, has never been implicated in mammalian cells. Here we show that mesaconate is synthesized in inflammatory macrophages from itaconate. We find that both, non-derivatized itaconate and mesaconate dampen the glycolytic activity to a similar extent, whereas only itaconate is able to repress tricarboxylic acid cycle activity and cellular respiration. In contrast to itaconate, mesaconate does not inhibit succinate dehydrogenase. Despite their distinct impact on metabolism, both metabolites exert similar immunomodulatory effects in pro-inflammatory macrophages, specifically a reduction of interleukin (IL)-6 and IL-12 secretion and an increase of CXCL10 production in a manner that is independent of NRF2 and ATF3. We show that a treatment with neither mesaconate nor itaconate impairs IL-1β secretion and inflammasome activation. In summary, our results identify mesaconate as an immunomodulatory metabolite in macrophages, which interferes to a lesser extent with cellular metabolism than itaconate.
536 _ _ |a 351 - Brain Function (POF4-351)
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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Inflammasomes
|2 NLM Chemicals
650 _ 7 |a Succinates
|2 NLM Chemicals
650 _ 7 |a itaconic acid
|0 Q4516562YH
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Inflammasomes
|2 MeSH
650 _ 2 |a Macrophages: drug effects
|2 MeSH
650 _ 2 |a Macrophages: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a RAW 264.7 Cells
|2 MeSH
650 _ 2 |a Succinates: metabolism
|2 MeSH
650 _ 2 |a Succinates: pharmacology
|2 MeSH
700 1 _ |a Henne, Antonia
|0 0000-0001-6870-5312
|b 1
700 1 _ |a Lauterbach, Mario
|b 2
700 1 _ |a Geißmar, Eike
|b 3
700 1 _ |a Nikolka, Fabian
|b 4
700 1 _ |a Kho, Celia
|b 5
700 1 _ |a Heinz, Alexander
|b 6
700 1 _ |a Dostert, Catherine
|b 7
700 1 _ |a Grusdat, Melanie
|b 8
700 1 _ |a Cordes, Thekla
|b 9
700 1 _ |a Härm, Janika
|b 10
700 1 _ |a Goldmann, Oliver
|b 11
700 1 _ |a Ewen, Anouk
|b 12
700 1 _ |a Verschueren, Charlène
|b 13
700 1 _ |a Blay-Cadanet, Julia
|b 14
700 1 _ |a Geffers, Robert
|0 0000-0003-4409-016X
|b 15
700 1 _ |a Garritsen, Hendrikus
|b 16
700 1 _ |a Kneiling, Manfred
|b 17
700 1 _ |a Holm, Christian K
|0 0000-0002-2655-3362
|b 18
700 1 _ |a Metallo, Christian M
|0 0000-0003-2404-3040
|b 19
700 1 _ |a Medina, Eva
|b 20
700 1 _ |a Abdullah, Zeinab
|b 21
700 1 _ |a Latz, Eicke
|0 P:(DE-2719)2000062
|b 22
|u dzne
700 1 _ |a Brenner, Dirk
|0 0000-0001-8979-1045
|b 23
700 1 _ |a Hiller, Karsten
|0 0000-0001-9322-5820
|b 24
773 _ _ |a 10.1038/s42255-022-00565-1
|g Vol. 4, no. 5, p. 524 - 533
|0 PERI:(DE-600)2933873-6
|n 5
|p 524 - 533
|t Nature metabolism
|v 4
|y 2022
|x 2522-5812
856 4 _ |u https://pub.dzne.de/record/164641/files/DZNE-2022-01171_Restricted.pdf
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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