FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3129125901> ?p ?o ?g. }

• W3129125901 abstract "Abstract The NLRP3 inflammasome is a multi-protein complex that regulates the protease caspase-1 and subsequent interleukin (IL)-1β release from cells of the innate immune system, or microglia in the brain, in response to infection or injury. Derivatives of the metabolites itaconate and fumarate, dimethyl itaconate (DMI), 4-octyl itaconate (4OI) and dimethyl fumarate (DMF), limit both expression of IL-1β, and IL-1β release following NLRP3 inflammasome activation. However, the direct effects of these metabolite derivatives on NLRP3 inflammasome responses in macrophages and microglia require further investigation. Using murine bone marrow-derived macrophages, mixed glia and organotypic hippocampal slice cultures (OHSCs), we demonstrate that DMI and 4OI pre-treatment limited IL-1β, IL-6 and tumor necrosis factor production in response to lipopolysaccharide (LPS) priming, as well as inhibiting subsequent NLRP3 inflammasome activation. DMI, 4OI, DMF and monomethyl fumarate (MMF), another fumarate derivative, also directly inhibited biochemical markers of NLRP3 activation in LPS-primed macrophages, mixed glia and OHSCs, including ASC speck formation, caspase-1 activation, gasdermin D cleavage and IL-1β release. Finally, DMF, an approved treatment for multiple sclerosis, as well as DMI, 4OI and MMF, inhibited NLRP3 activation in macrophages in response to the phospholipid lysophosphatidylcholine, which is used to induce demyelination, suggesting a possible mechanism of action for DMF in multiple sclerosis through NLRP3 inhibition. Together, these findings reveal the importance of immunometabolic regulation for both the priming and activation steps of NLRP3 activation in macrophages and microglia. Furthermore, we highlight itaconate and fumarate derivatives as a potential therapeutic option in NLRP3-driven diseases, including in the brain. Summary statement We show that itaconate and fumarate derivatives inhibit both the priming and activation steps of NLRP3 inflammasome responses in macrophages and microglia, revealing the importance of immunometabolic NLRP3 regulation." @default.
• W3129125901 created "2021-02-15" @default.
• W3129125901 creator A5006384918 @default.
• W3129125901 creator A5009694951 @default.
• W3129125901 creator A5022583171 @default.
• W3129125901 creator A5024443255 @default.
• W3129125901 creator A5057854608 @default.
• W3129125901 date "2021-02-02" @default.
• W3129125901 modified "2023-10-18" @default.
• W3129125901 title "Itaconate and fumarate derivatives exert a dual inhibitory effect on canonical NLRP3 activation in macrophages and microglia" @default.
• W3129125901 cites W1680053970 @default.
• W3129125901 cites W1889195978 @default.
• W3129125901 cites W1967838438 @default.
• W3129125901 cites W1978094617 @default.
• W3129125901 cites W2009004909 @default.
• W3129125901 cites W2028479792 @default.
• W3129125901 cites W2042851093 @default.
• W3129125901 cites W2050259192 @default.
• W3129125901 cites W2054275187 @default.
• W3129125901 cites W2079054696 @default.
• W3129125901 cites W2079882002 @default.
• W3129125901 cites W2080827095 @default.
• W3129125901 cites W2089532303 @default.
• W3129125901 cites W2093009907 @default.
• W3129125901 cites W2095547757 @default.
• W3129125901 cites W2096317294 @default.
• W3129125901 cites W2097080185 @default.
• W3129125901 cites W2119098586 @default.
• W3129125901 cites W2126384811 @default.
• W3129125901 cites W2130989367 @default.
• W3129125901 cites W2135339492 @default.
• W3129125901 cites W2140637559 @default.
• W3129125901 cites W2143310289 @default.
• W3129125901 cites W2175794645 @default.
• W3129125901 cites W2317391245 @default.
• W3129125901 cites W2336862132 @default.
• W3129125901 cites W2364675877 @default.
• W3129125901 cites W2400239628 @default.
• W3129125901 cites W2419603827 @default.
• W3129125901 cites W2464206716 @default.
• W3129125901 cites W2527001605 @default.
• W3129125901 cites W2539358755 @default.
• W3129125901 cites W2587237321 @default.
• W3129125901 cites W2592459614 @default.
• W3129125901 cites W2605685784 @default.
• W3129125901 cites W2766317007 @default.
• W3129125901 cites W2790085444 @default.
• W3129125901 cites W2791444686 @default.
• W3129125901 cites W2794813666 @default.
• W3129125901 cites W2794844698 @default.
• W3129125901 cites W2797967513 @default.
• W3129125901 cites W2808342347 @default.
• W3129125901 cites W2894687190 @default.
• W3129125901 cites W2898666595 @default.
• W3129125901 cites W2902713146 @default.
• W3129125901 cites W2914298128 @default.
• W3129125901 cites W2918626547 @default.
• W3129125901 cites W2919002166 @default.
• W3129125901 cites W2936917182 @default.
• W3129125901 cites W2945167793 @default.
• W3129125901 cites W2970602413 @default.
• W3129125901 cites W2988457676 @default.
• W3129125901 cites W3007536995 @default.
• W3129125901 cites W3023714202 @default.
• W3129125901 cites W3026294000 @default.
• W3129125901 cites W3026959467 @default.
• W3129125901 cites W3033548100 @default.
• W3129125901 cites W3048446878 @default.
• W3129125901 cites W3080259742 @default.
• W3129125901 cites W3086776179 @default.
• W3129125901 cites W3091428163 @default.
• W3129125901 cites W3092041441 @default.
• W3129125901 cites W4211217520 @default.
• W3129125901 cites W621508424 @default.
• W3129125901 doi "https://doi.org/10.1101/2021.02.01.429180" @default.
• W3129125901 hasPublicationYear "2021" @default.
• W3129125901 type Work @default.
• W3129125901 sameAs 3129125901 @default.
• W3129125901 citedByCount "1" @default.
• W3129125901 countsByYear W31291259012022 @default.
• W3129125901 crossrefType "posted-content" @default.
• W3129125901 hasAuthorship W3129125901A5006384918 @default.
• W3129125901 hasAuthorship W3129125901A5009694951 @default.
• W3129125901 hasAuthorship W3129125901A5022583171 @default.
• W3129125901 hasAuthorship W3129125901A5024443255 @default.
• W3129125901 hasAuthorship W3129125901A5057854608 @default.
• W3129125901 hasBestOaLocation W31291259011 @default.
• W3129125901 hasConcept C139964883 @default.
• W3129125901 hasConcept C170493617 @default.
• W3129125901 hasConcept C185592680 @default.
• W3129125901 hasConcept C187831198 @default.
• W3129125901 hasConcept C203014093 @default.
• W3129125901 hasConcept C2776819417 @default.
• W3129125901 hasConcept C2776914184 @default.
• W3129125901 hasConcept C2777209026 @default.
• W3129125901 hasConcept C2778754761 @default.
• W3129125901 hasConcept C2779830541 @default.
• W3129125901 hasConcept C2780640218 @default.
• W3129125901 hasConcept C55493867 @default.
• W3129125901 hasConcept C86803240 @default.

• next