About: The Immunomodulatory Metabolite Itaconate Modifies NLRP3 and Inhibits Inflammasome Activation

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About: The Immunomodulatory Metabolite Itaconate Modifies NLRP3 and Inhibits Inflammasome Activation Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	The Immunomodulatory Metabolite Itaconate Modifies NLRP3 and Inhibits Inflammasome Activation
Creator	Hughes, Mark Angiari, Stefano Banahan, Kathy Corcoran, Sarah Fischer, Roman Hester, Svenja Hooftman, Alexander Irvine, Alan Ling, Chris Mcgettrick, Anne O'neill, Luke Runtsch, Marah Ruzek, Melanie Slivka, Peter
Source	Elsevier; Medline; PMC
abstract	The Krebs cycle-derived metabolite itaconate is highly upregulated in inflammatory macrophages and exerts immunomodulatory effects through cysteine modifications on target proteins. The NLRP3 inflammasome, which cleaves IL-1β, IL-18, and gasdermin D, must be tightly regulated to avoid excessive inflammation. Here we provide evidence that itaconate modifies NLRP3 and inhibits inflammasome activation. Itaconate and its derivative, 4-octyl itaconate (4-OI), inhibited NLRP3 inflammasome activation, but not AIM2 or NLRC4. Conversely, NLRP3 activation was increased in itaconate-depleted Irg1(−/−) macrophages. 4-OI inhibited the interaction between NLRP3 and NEK7, a key step in the activation process, and “dicarboxypropylated” C548 on NLRP3. Furthermore, 4-OI inhibited NLRP3-dependent IL-1β release from PBMCs isolated from cryopyrin-associated periodic syndrome (CAPS) patients, and reduced inflammation in an in vivo model of urate-induced peritonitis. Our results identify itaconate as an endogenous metabolic regulator of the NLRP3 inflammasome and describe a process that may be exploited therapeutically to alleviate inflammation in NLRP3-driven disorders.
has issue date	2020-08-12(xsd:dateTime)
bibo:doi	10.1016/j.cmet.2020.07.016
bibo:pmid	32791101
has license	no-cc
sha1sum (hex)	a759c35d627e65b3ff2debc68c5ff1a7c65a4982
schema:url	https://doi.org/10.1016/j.cmet.2020.07.016
resource representing a document's title	The Immunomodulatory Metabolite Itaconate Modifies NLRP3 and Inhibits Inflammasome Activation
has PubMed Central identifier	PMC7422798
has PubMed identifier	32791101
schema:publication	Cell Metab
resource representing a document's body	covid:a759c35d627e65b3ff2debc68c5ff1a7c65a4982#body_text
is schema:about of	named entity 'inflammasome' covid:arg/a759c35d627e65b3ff2debc68c5ff1a7c65a4982 named entity 'activation' named entity 'itaconate' named entity 'IL-1b' named entity 'NLRP3' named entity 'FlowJo' named entity 'inflammasomes' named entity 'sodium orthovanadate' named entity 'S3G' named entity 'immune complexes' named entity 'CD45' named entity 'unsaturated' named entity 'cyclised' named entity 'immune complexes' named entity 'Bioinformatics' named entity 'Addgene' named entity 'NLRP3' named entity 'NLRP3' named entity 'caspase-4' named entity 'gradient elution' named entity 'IL-1b' named entity 'pyroptosis' named entity 'IL-18' named entity 'negative ion' named entity 'itaconate' named entity 'PBS' named entity 'insoluble' named entity 'PBS' named entity 'itaconate' named entity 'non-significant' named entity 'Biochemistry' named entity 'FACS' named entity 'octyl' named entity 'IgG antibody' named entity 'NLRP3' named entity 'S1C' named entity 'inflammasome' named entity 'NLRP3' named entity 'NLRP3' named entity 'carboxy-terminal' named entity 'protein' named entity 'pyroptosis' named entity 'NLRP3' named entity 'LPS' named entity 'crosslinking' named entity 'NLRC4' named entity 'inflammasome' named entity 'murine' named entity 'mice' named entity 'Oxidation' named entity 'Escherichia coli' named entity 'caspase-1' named entity 'DMEM' named entity 'cell lysate' named entity 'NLRP3' named entity 'HEPES' named entity 'mononuclear cells' named entity 'itaconate' named entity 'organ' named entity 'centrifuged' named entity 'erythroid' named entity 'streptomycin' named entity 'octyl' named entity 'supernatant' named entity 'RPMI' named entity 'IL-1b' named entity 'confidence interval'

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