Neuronal accumulation of peroxidated lipids promotes demyelination and neurodegeneration though the activation of the microglial NLRP3 inflammasome
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ABSTRACT:
PROVIDER: PRJNA760949 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15725384_1.fastq.gz | Fastqsanger.gz | |||
| SRR15725384_2.fastq.gz | Fastqsanger.gz | |||
| SRR15725385_1.fastq.gz | Fastqsanger.gz | |||
| SRR15725385_2.fastq.gz | Fastqsanger.gz | |||
| SRR15725386_1.fastq.gz | Fastqsanger.gz |
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2021-09-08 | GSE183483 | GEO
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Project description:The immune system may respond to engineered nanomaterials (ENM) through inflammatory reactions. The NLRP3 inflammasome responds to a wide range of ENM, and its activation is associated with various inflammatory diseases. The objective of the study was to compare the effects of gold ENM of different shapes on NLRP3 inflammasome activation and related signalling pathways. Differentiated THP-1 cells (wildtype, ASC- or NLRP3-deficient), were exposed to PEGylated gold nanorods, nanostars, and nanospheres. Exposed cells were subjected to gene expression analysis. Nanorods, but not nanostars or nanospheres, showed NLRP3 inflammasome activation. ASC- or NLRP3-deficient cells did not show this effect. Gold nanorod-induced NLRP3 inflammasome activation was accompanied by downregulated sterol/cholesterol biosynthesis, oxidative phosphorylation, and purinergic receptor signalling. In conclusion, the shape and surface chemistry of gold nanoparticles determine NLRP3 inflammasome activation.
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Project description:The NLRP3 inflammasome is a multi-protein complex that triggers the activation of the inflammatory protein caspase-1 and the maturation of the cytokine IL-1 in response to microbes and other danger signals in host cells. Here, we sought a deeper understanding of how the NLRP3 inflammasome is regulated. We found that inflammasome activation induced the Src family kinase Lyn to phosphorylate NLRP3 at Tyr918, and that this phosphorylation of NLRP3 correlated with a subsequent increase in its ubiquitination, which facilitated its proteasome-mediated degradation. NLRP3 tyrosine phosphorylation and ubiquitination was abrogated in Lyn-deficient macrophages, which produced increased amounts of IL-1. Furthermore, mice lacking Lyn were highly susceptible to LPS-induced septic shock in an NLRP3-dependent manner. Our data demonstrate that Lyn-mediated tyrosine phosphorylation of NLRP3 is a prerequisite for its ubiquitination, thus dampening NLRP3 inflammasome activity.
2022-05-19 | PXD028582 | Pride
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2022-11-29 | PXD033497 | Pride