2018
DOI: 10.1038/nature25986
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Abstract: The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood. Here we show that itaconate is required for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KE… Show more

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Cited by 1,107 publications
(1,330 citation statements)
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“…Chemicals, reagents and antibodies OI was synthesized by Min-de Biotech (Suzhou, China) based on a previously described protocol [16]. Lipopolysaccharide (LPS) and puromycin were purchased from Sigma-Aldrich Co. (St. Louis, MO).…”
Section: Methodsmentioning
confidence: 99%
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“…Chemicals, reagents and antibodies OI was synthesized by Min-de Biotech (Suzhou, China) based on a previously described protocol [16]. Lipopolysaccharide (LPS) and puromycin were purchased from Sigma-Aldrich Co. (St. Louis, MO).…”
Section: Methodsmentioning
confidence: 99%
“…We first tested the potential effect of OI, the cell-permeable derivative of itaconate [16], on Nrf2 signaling in THP-1 human macrophages [31,32]. By performing the coimmunoprecipitation assay, we showed that treatment with OI (25 μM, 2 h) disrupted the association between Keap1-Nrf2 in THP-1 cells (Fig.…”
Section: Oi Activated Nrf2 Signaling In Thp-1 Cells and Sle Patient-dmentioning
confidence: 99%
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