FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3138180770> ?p ?o ?g. }

• W3138180770 endingPage "4548" @default.
• W3138180770 startingPage "4531" @default.
• W3138180770 abstract "Background: Peroxisome proliferator-activated receptor gamma (PPARγ) has the ability to counter Th17 responses, but the full mechanisms remain elusive. Herein, we aimed to elucidate this process in view of cellular metabolism, especially glutaminolysis. Methods: MTT, CCK-8, Annexin V-FITC/PI staining or trypan blue exclusion assays were used to analyze cytotoxicity. Flow cytometry and Q-PCR assays were applied to determine Th17 responses. The detection of metabolite levels using commercial kits and rate-limiting enzyme expression using western blotting assays was performed to illustrate the metabolic activity. ChIP assays were used to examine H3K4me3 modifications. Mouse models of dextran sulfate sodium (DSS)-induced colitis and house dust mite (HDM)/lipopolysaccharide (LPS)-induced asthma were established to confirm the mechanisms studied in vitro. Results: The PPARγ agonists rosiglitazone and pioglitazone blocked glutaminolysis but not glycolysis under Th17-skewing conditions, as indicated by the detection of intracellular lactate and α-KG and the fluorescence ratios of BCECF-AM. The PPARγ agonists prevented the utilization of glutamine and thus directly limited Th17 responses even when Foxp3 was deficient. The mechanisms were ascribed to restricted conversion of glutamine to glutamate by reducing the expression of the rate-limiting enzyme GLS1, which was confirmed by GLS1 overexpression. Replenishment of α-KG and 2-HG but not succinate weakened the effects of PPARγ agonists, and α-KG-promoted Th17 responses were dampened by siIDH1/2. Inhibition of KDM5 but not KDM4/6 restrained the inhibitory effect of PPARγ agonists on IL-17A expression, and the H3K4me3 level in the promoter and CNS2 region of the il-17 gene locus down-regulated by PPARγ agonists was rescued by 2-HG and GLS1 overexpression. However, the limitation of PPARγ agonists on the mRNA expression of RORγt was unable to be stopped by 2-HG but was attributed to GSH/ROS signals subsequent to GLS1. The exact role of PPARγ was proved by GW9662 or PPARγ knockout, and the mechanisms for PPARγ-inhibited Th17 responses were further confirmed by GLS1 overexpression in vivo. Conclusion: PPARγ agonists repressed Th17 responses by counteracting GLS1-mediated glutaminolysis/2-HG/H3K4me3 and GSH/ROS signals, which is beneficial for Th17 cell-related immune dysregulation." @default.
• W3138180770 created "2021-03-29" @default.
• W3138180770 creator A5014130007 @default.
• W3138180770 creator A5018242981 @default.
• W3138180770 creator A5048971530 @default.
• W3138180770 creator A5051442598 @default.
• W3138180770 creator A5064432127 @default.
• W3138180770 creator A5074904736 @default.
• W3138180770 creator A5081641076 @default.
• W3138180770 date "2021-01-01" @default.
• W3138180770 modified "2023-09-29" @default.
• W3138180770 title "The role of GLS1-mediated glutaminolysis/2-HG/H3K4me3 and GSH/ROS signals in Th17 responses counteracted by PPARγ agonists" @default.
• W3138180770 cites W1840785378 @default.
• W3138180770 cites W1994196052 @default.
• W3138180770 cites W2003398132 @default.
• W3138180770 cites W2027277087 @default.
• W3138180770 cites W2034575413 @default.
• W3138180770 cites W2041924570 @default.
• W3138180770 cites W2092345398 @default.
• W3138180770 cites W2119800629 @default.
• W3138180770 cites W2126538938 @default.
• W3138180770 cites W2128233861 @default.
• W3138180770 cites W2133300386 @default.
• W3138180770 cites W2144502480 @default.
• W3138180770 cites W2162873738 @default.
• W3138180770 cites W2164749297 @default.
• W3138180770 cites W2513413220 @default.
• W3138180770 cites W2554062701 @default.
• W3138180770 cites W2569549188 @default.
• W3138180770 cites W2603846877 @default.
• W3138180770 cites W2607326270 @default.
• W3138180770 cites W2625418525 @default.
• W3138180770 cites W2741802290 @default.
• W3138180770 cites W2748925127 @default.
• W3138180770 cites W2763989125 @default.
• W3138180770 cites W2764070380 @default.
• W3138180770 cites W2770082188 @default.
• W3138180770 cites W2781725704 @default.
• W3138180770 cites W2783692413 @default.
• W3138180770 cites W2790735034 @default.
• W3138180770 cites W2792396848 @default.
• W3138180770 cites W2792797672 @default.
• W3138180770 cites W2804426940 @default.
• W3138180770 cites W2871651193 @default.
• W3138180770 cites W2889319816 @default.
• W3138180770 cites W2892039303 @default.
• W3138180770 cites W2898875160 @default.
• W3138180770 cites W2899010137 @default.
• W3138180770 cites W2901842078 @default.
• W3138180770 cites W2905250717 @default.
• W3138180770 cites W2921191661 @default.
• W3138180770 cites W2924408078 @default.
• W3138180770 cites W2946616105 @default.
• W3138180770 cites W2947844033 @default.
• W3138180770 cites W2956048237 @default.
• W3138180770 cites W2966588036 @default.
• W3138180770 cites W2983049339 @default.
• W3138180770 cites W2986108390 @default.
• W3138180770 cites W2998860831 @default.
• W3138180770 cites W3003146742 @default.
• W3138180770 cites W3081849955 @default.
• W3138180770 doi "https://doi.org/10.7150/thno.54803" @default.
• W3138180770 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7977454" @default.
• W3138180770 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33754076" @default.
• W3138180770 hasPublicationYear "2021" @default.
• W3138180770 type Work @default.
• W3138180770 sameAs 3138180770 @default.
• W3138180770 citedByCount "23" @default.
• W3138180770 countsByYear W31381807702021 @default.
• W3138180770 countsByYear W31381807702022 @default.
• W3138180770 countsByYear W31381807702023 @default.
• W3138180770 crossrefType "journal-article" @default.
• W3138180770 hasAuthorship W3138180770A5014130007 @default.
• W3138180770 hasAuthorship W3138180770A5018242981 @default.
• W3138180770 hasAuthorship W3138180770A5048971530 @default.
• W3138180770 hasAuthorship W3138180770A5051442598 @default.
• W3138180770 hasAuthorship W3138180770A5064432127 @default.
• W3138180770 hasAuthorship W3138180770A5074904736 @default.
• W3138180770 hasAuthorship W3138180770A5081641076 @default.
• W3138180770 hasBestOaLocation W31381807701 @default.
• W3138180770 hasConcept C101762097 @default.
• W3138180770 hasConcept C104317684 @default.
• W3138180770 hasConcept C150194340 @default.
• W3138180770 hasConcept C170493617 @default.
• W3138180770 hasConcept C185592680 @default.
• W3138180770 hasConcept C187345961 @default.
• W3138180770 hasConcept C20251656 @default.
• W3138180770 hasConcept C2778160063 @default.
• W3138180770 hasConcept C2780914512 @default.
• W3138180770 hasConcept C48349386 @default.
• W3138180770 hasConcept C502942594 @default.
• W3138180770 hasConcept C55493867 @default.
• W3138180770 hasConcept C62231903 @default.
• W3138180770 hasConcept C86803240 @default.
• W3138180770 hasConcept C95444343 @default.
• W3138180770 hasConceptScore W3138180770C101762097 @default.
• W3138180770 hasConceptScore W3138180770C104317684 @default.
• W3138180770 hasConceptScore W3138180770C150194340 @default.

• next