PLCG2 regulates endocannabinoid and eicosanoid networks in innate immune cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA747300 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15178941_1.fastq.gz | Fastqsanger.gz | |||
| SRR15178941_2.fastq.gz | Fastqsanger.gz | |||
| SRR15178942_1.fastq.gz | Fastqsanger.gz | |||
| SRR15178942_2.fastq.gz | Fastqsanger.gz | |||
| SRR15178943_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Human genetic studies have pointed to a prominent role for innate immunity and lipid pathways in human immunological and neurodegenerative disorders. Our understanding of the composition and function of immunomodulatory lipid networks in innate immune cells, however, remains incomplete. Here, we show that phospholipase C gamma 2 (PLCγ2 or PLCG2) – mutations in which are associated with autoinflammatory disorders and Alzheimer’s disease – serves as a principal source of diacylglycerol (DAG) pools that are converted into a cascade of bioactive endocannabinoid (eCB) and eicosanoid lipids by DAG lipase (DAGL) and monoacylglycerol lipase (MGLL) enzymes in innate immune cells. We show that this lipid network is tonically stimulated by disease-relevant human mutations in PLCγ2, as well as Fc receptor activation in primary human and mouse macrophages. Genetic disruption of PLCγ2 in mouse microglia suppressed DAGL/MGLL-mediated eCB-eicosanoid crosstalk and also caused widespread transcriptional and proteomic changes, including the reorganization of immune-relevant lipid pathways reflected in reductions in DAGLB and elevations in PLA2G4A. Despite these changes, Plcg2-/- mice showed generally normal pro-inflammatory cytokine responses to lipopolysaccharide treatment, instead displaying a more restricted deficit in microglial activation that included impairments in prostaglandin production and CD68 expression. Our findings enhance the understanding of PLCγ2 function in innate immune cells, delineating a role in crosstalk with endocannabinoid/eicosanoid pathways and modulation of subsets of cellular responses to inflammatory stimuli.
2021-10-04 | GSE180274 | GEO
Project description:Human genetic studies have pointed to a prominent role for innate immunity and lipid pathways in human immunological and neurodegenerative disorders. Our understanding of the composition and function of immunomodulatory lipid networks in innate immune cells, however, remains incomplete. Here, we show that phospholipase C gamma 2 (PLCγ2 or PLCG2) – mutations in which are associated with autoinflammatory disorders and Alzheimer’s disease – serves as a principal source of diacylglycerol (DAG) pools that are converted into a cascade of bioactive endocannabinoid (eCB) and eicosanoid lipids by DAG lipase (DAGL) and monoacylglycerol lipase (MGLL) enzymes in innate immune cells. We show that this lipid network is tonically stimulated by disease-relevant human mutations in PLCγ2, as well as Fc receptor activation in primary human and mouse macrophages. Genetic disruption of PLCγ2 in mouse microglia suppressed DAGL/MGLL-mediated eCB-eicosanoid crosstalk and also caused widespread transcriptional and proteomic changes, including the reorganization of immune-relevant lipid pathways reflected in reductions in DAGLB and elevations in PLA2G4A. Despite these changes, Plcg2-/- mice showed generally normal pro-inflammatory cytokine responses to lipopolysaccharide treatment, instead displaying a more restricted deficit in microglial activation that included impairments in prostaglandin production and CD68 expression. Our findings enhance the understanding of PLCγ2 function in innate immune cells, delineating a role in crosstalk with endocannabinoid/eicosanoid pathways and modulation of subsets of cellular responses to inflammatory stimuli.
2021-10-05 | PXD027350 | Pride
Project description:Diacylglycerol lipase-beta (DAGLB) serves as a principal 2-arachidonoylglycerol (2-AG) biosynthetic enzyme regulating endocannabinoid and eicosanoid metabolism in immune cells including macrophages and dendritic cells. Genetic or pharmacological inactivation of DAGLb ameliorates inflammation and hyper-nociception in preclinical models of pathogenic pain. These beneficial effects have been assigned principally to reductions in downstream pro-inflammatory lipid signaling, leaving alternative mechanisms of regulation largely underexplored. Here, we apply quantitative chemical- and phospho-proteomics to discover that disruption of DAGLb in primary macrophages leads to LKB1-AMPK signaling activation, resulting in reprogramming of the phosphoproteome and bioenergetics. Notably, AMPK inhibition reversed the antinociceptive effects of DAGLb blockade, thereby directly supporting DAGLβ-AMPK crosstalk in vivo. Our findings uncover signaling between endocannabinoid biosynthetic enzymes and ancient energy sensing kinases to mediate cell biological and pain responses.
2024-01-02 | GSE249312 | GEO
Project description:Diacylglycerol lipase-beta (DAGLβ) serves as a principal 2-arachidonoylglycerol (2-AG) biosynthetic enzyme regulating endocannabinoid and eicosanoid metabolism in immune cells including macrophages and dendritic cells. Genetic or pharmacological inactivation of DAGLβ ameliorates inflammation and hyper-nociception in preclinical models of pathogenic pain. These beneficial effects have been assigned principally to reductions in downstream proinflammatory lipid signaling, leaving alternative mechanisms of regulation largely underexplored. Here, we apply quantitative chemical- and phospho-proteomics to find that disruption of DAGLβ in primary macrophages leads to LKB1–AMPK signaling activation, resulting in reprogramming of the phosphoproteome and bioenergetics. Notably, AMPK inhibition reversed the antinociceptive effects of DAGLβ blockade, thereby directly supporting DAGLβ–AMPK crosstalk in vivo. Our findings uncover signaling between endocannabinoid biosynthetic enzymes and ancient energy-sensing kinases to mediate cell biological and pain responses.
2024-01-02 | PXD047413 | Pride
Project description:Endocannabinoid signaling plays a key role in multiple events in female reproduction. In this investigation, we discovered an interesting phenomenon that mice with either elevated or silenced endocannabinoid signaling show similar defects in multiple pregnancy events, including preimplantation embryo development. To unravel the underlying mechanisms, microarray studies were was conducted using RNAs collected from WT, Cnr1-/- and Faah-/- mouse blastocysts on day 4 of pregnancy. The results show that about 100 genes showed unidirectional changes under either elevated or silenced endocannabinoid signaling. Analysis of functional grouping of these genes revealed that multiple biological functions and pathways are affected under aberrant endocannabinoid signaling, including cell migration. Several genes from the microarray data were confirmed by quantitative RT-PCR. Cell motility assays validated the predicted compromised cell migration in Cnr1-/- and Faah-/- trophoblast stem cells. This study provides molecular basis for biphasic effects of endocannabinoid signaling in female reproduction
2012-07-26 | GSE36399 | GEO
Project description:Endocannabinoid signaling plays a key role in multiple events in female reproduction. In this investigation, we discovered an interesting phenomenon that mice with either elevated or silenced endocannabinoid signaling show similar defects in multiple pregnancy events, including preimplantation embryo development. To unravel the underlying mechanisms, microarray studies were was conducted using RNAs collected from WT, Cnr1-/- and Faah-/- mouse blastocysts on day 4 of pregnancy. The results show that about 100 genes showed unidirectional changes under either elevated or silenced endocannabinoid signaling. Analysis of functional grouping of these genes revealed that multiple biological functions and pathways are affected under aberrant endocannabinoid signaling, including cell migration. Several genes from the microarray data were confirmed by quantitative RT-PCR. Cell motility assays validated the predicted compromised cell migration in Cnr1-/- and Faah-/- trophoblast stem cells. This study provides molecular basis for biphasic effects of endocannabinoid signaling in female reproduction To generate Cnr1-/-, Faah-/- and WT embryos, mutant and WT females were mated with males of the same genotypes. On day 4 of pregnancy at 1500h, embryos were collected from oviducts and uteri of pregnant females, because Cnr1-/- and Faah-/- females show aberrant oviductal transport of embryos. As expected, WT embryos were mostly at the blastocyst stage and all of them were collected from uteri. However, Cnr1-/- and Faah-/- females had higher percentages of embryos at the morula stage, and some of them were still in the oviduct. Since gene expression profiles greatly vary depending on the embryonic development stage, morulae were not included in gene expression analysis; only RNAs from blastocysts were used to better understand the effects solely arising from disrupted cannabinoid signaling in blastocysts.
2012-07-25 | E-GEOD-36399 | biostudies-arrayexpress
Project description:Differential expression analysis in Plcg2-inactivated mouse model identified inflammation-related genes and pathways.
2022-02-07 | GSE195650 | GEO
Project description:Differential expression analysis identified inflammation-related pathways in AD samples with reduced PLCG2 expression
2025-01-01 | GSE196502 | GEO
Project description:Eicosanoid and Eicosanoid-Related Inflammatory Mediators and Exercise Intolerance in Heart Failure with Preserved Ejection Fraction
2023-08-28 | MSV000092775 | MassIVE
Project description:To analyse the effect of endocannabinoid AEA on the expression of inflammation related miRNAs in HIV1 TAT activated Normal Human Astrocytes.
2023-08-05 | GSE210095 | GEO