Identification of the target gene expression of peptide SK56 in human macrophage cells during pyroptosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE240889 | GEO | 2023/10/22
REPOSITORIES: GEO
Similar Datasets
Project description:To gain insight into the peptide SK56 target gene profile in macrophage cells, we performed RNA-seq analysis in PMA-differentiated THP-1 cells upon LPS+nigericin with or without SK56, to analyze the signaling pathway of cell pyroptosis blocked by SK56.
2024-06-21 | PXD053323 |
Project description:Inflammasome activation in macrophages induces the release of EVs, however, the effect of these inflammasome-induced EVs on recipient cells is poorly characterized. To characterize the effect EVs released upon LPS + nigericin stimulation, we performed 3' sequencing on the recipient cells (NLRP3 KO THP-1 macrophages and NLRP3 KO THP-1 macrophages that have been reconstituted with NLRP3 to resemble the WT). As controls, RNA isolated from EVs themselves or LPS- or nigericin-treated cells were subjected to 3' sequencing.
2021-07-26 | GSE180707 | GEO
Project description:The experiments were done using an Orbitrap Fusion or an Orbitrap Fusion Lumos mass spectrometer. Multiplexing was achieved using either TMT10 or TMT11 reagents and the SPS-MS3 method. Basic pH reversed-phase chromatography (bRPLC) was used for off-line pre-fractionation; 12 fractions were analyzed for proteome mappings (PMID: 26700037) and 24 fractions plus a phosphotyrosine-enriched sample for phosphoproteome mappings (PMID: 31606085). Phosphoproteome mappings were done using both HCD fragmentation with Orbitrap fragment ion detection and CID fragmentation with ion trap fragment ion detection (PMID: 29487189, PMID: 31606085). If multiple TMT sets were required to analyze all samples from an experiment two bridge channels pooled from all samples was used to connect the data from the individual TMT sets (PMID: 28892078).
Five proteomics experiments are described in the paper:
(i) 1. Quantitative proteomics of fully polarized macrophages after 4 days of treatment with IL4 or IFNgamma/LPS to determine global proteome landscape of fully polarized THP-1-derived M1-type versus M2a-type macrophages:
Proteome mapping on Orbitrap Fusion (one TMT set)
RAW files: Marneros_4DayTreatment_proteome_fraction01 to ...fraction12
8 samples
Labeling: PMA.1 (126), PMA.2 (127n), IL4.1 (127c), IL4.2 (128n), ILJQ1.1 (128c), ILJQ1.2 (129n), IFNgamma.1 (129c), IFNgamma.2 (130n)
(ii) Time-course quantitative proteomics during the first 24 hours after induction of macrophage polarization in THP-1-derived macrophages to identify protein changes associated with M1-type (IFNgamma/LPS-induced) versus M2a-type (IL-4-induced) polarization:
Proteome mapping on Orbitrap Fusion (three TMT sets: set01, set02, set03)
RAW files:
Marneros_timecourse_proteome_TMTset01_fraction01 to ...fraction12
Marneros_timecourse_proteome_TMTset02_fraction01 to ...fraction12
Marneros_timecourse_proteome_TMTset03_fraction01 to ...fraction12
22 samples
Labeling:
set01; bridge 1 (126), PMA 0min (127n), PMA 10min (127c), PMA 30min (128n), PMA 1h (128c), PMA 2h (129n), PMA 4h (129c), PMA 8h (130n), PMA 24h (130c), bridge 2 (131n)
set02; bridge 1 (126), IL4 10min (127n), IL4 30min (127c), IL4 1h (128n), IL4 2h (128c), IL4 4h (129n), IL4 8h (129c), IL4 24h (130n), IFN 10min (130c), bridge 2 (131n)
set03; bridge 1 (126), IFN 30min (127n), IFN 1h (127c), IFN 2h (128n), IFN 4h (128c), IFN 8h (129n), IFN 24h (129c), bridge 2 (131n)
(iii) Time-course quantitative phosphoproteomics during the first 24 hours after induction of macrophage polarization in THP-1-derived macrophages to identify phosphorylation events associated with M1-type (IFNgamma/LPS-induced) versus M2a-type (IL-4-induced) polarization (same time points as in group 2):
Phosphoproteome mapping on Orbitrap Fusion (three TMT sets: set01, set02, set03)
RAW files:
Marneros_timecourse_phospho_TMTset01_fraction01 to ...fraction06, ...fraction08 to ...fraction24, ...pY
Marneros_timecourse_phospho_TMTset02_fraction01 to ...fraction12, ...fraction16 to ...fraction24, ...pY
Marneros_timecourse_phospho_TMTset03_fraction01 to ...fraction24, ...pY
The following RAW files gave no phosphopeptide quantifications (they are no included in the group of provided RAW files): set01_fraction07, set02_fraction13, set02_fraction14, set02_fraction15.
22 samples
Labeling: as in (ii)
(iv) Quantitative proteomics to assess the effects of the B-Raf inhibitor GDC-0879 or of the MEK inhibitor trametinib on IL-4-induced M2-type polarization and IFNgamma/LPS-induced M1-type polarization on THP-1-derived macrophages after 24 hours of treatment:
Proteome mapping on Orbitrap Fusion (one TMT set)
RAW files: Marneros_BRAF_inhibitor_proteine_fraction01 to ...fraction12
11 samples
Labeling: IL4 1 (131c), IL4 2 (127n), IL4+GDC 1 (131n), IL4+GDC 2 (128n), IL4+TRAM 1 (130c), IL4+TRAM 2 (129n), IFNgamma+LPS 1 (130n), IFNgamma+LPS 2 (127c), IFNgamma+LPS+TRAM 1 (126), IFNgamma+LPS+TRAM 2(129c), IFNgamma+LPS+GDC (128c)
(v) Quantitative phosphoproteomics to assess the effects of the B-Raf inhibitor GDC-0879 on IL-4-induced M2-type polarization and IFNgamma/LPS-induced M1-type polarization on THP-1-derived macrophages after 24 hours of treatment:
Phosphoproteome mapping on Orbitrap Fusion Lumos (one TMT set)
RAW files: Marneros_BRAF_inhibitor_phospho_fraction01 to ...fraction24, ...pY
7 samples
Labeling: IL4 1 (131c), IL4 2 (127n), IL4+GDC 1 (130n), IL4+GDC 2 (128n), IFNgamma+LPS 1 (128c), IFNgamma+LPS 2 (127c), IFNgamma+LPS+GDC (130c)
2019-12-10 | MSV000084672 | MassIVE
Project description:THP-1 monocytes were differentiated, via PMA treatment, to macrophages. THP-1 macrophages were then treated with a mixed-oxysterol treatment (7-ketocholesterol and 7beta-hydroxycholesterol) for 24 hours. The mixed-oxysterol treatment was mixed to a ratio that represents the cytotoxic oxysterol content of human atherosclerotic plaque. Control and treated macrophages were analysed using both 2-DE with peptide mass-fingerprinting and tandem-mass spectrometry.
2017-03-15 | PXD004304 | Pride
Project description:Identification of the target gene expression of peptide SK56 in human macrophage cells during pyroptosis
| PRJNA1005651 | ENA
Project description:The objective of the study was to evaluate transcriptional response of endotoxin-stimulated human monocytic cells in presence or absence of host defense peptide LL-37 at low physiologically relevant concentrations. Human monocytic cells THP-1 were stimulated with LPS (10ng/ml) in presence or absence of LL-37 (5 ug/ml), as well as with the peptide alone, for 4 hours. The trends of LPS-induced altered gene expression in presence of the peptide were further validated by quantitative real-time PCR.
2006-12-07 | E-FPMI-6 | biostudies-arrayexpress
Project description:Gasdermin D (GSDMD) is the executioner of pyroptosis, which is important for host defense against pathogen infection. After activation, caspase-mediated cleavage of GSDMD liberates an N-terminal fragment (GSDMD-NT), which oligomerizes and forms pores in the plasma membrane, leading to cell death and subsequent release of proinflammatory cytokines. How this process is spatiotemporally controlled to promote pyroptosis in cells has been a fundamental, unaddressed question. Here, we identify GSDMD as a substrate for reversible S-palmitoylation on cysteine 192 (Cys192) in response to lipopolysaccharide (LPS) stimulation. We found that the palmitoyl acyltransferase DHHC7palmitoylates GSDMD to direct its cleavage by caspases in pyroptosis by promoting the interaction of GSDMD and caspases. We further show that after GSDMD cleavage, palmitoylation of GSDMD-NTpromotes its plasma membrane translocation and binding, and then acyl protein thioesterase 2 (APT2) depalmitoylates GSDMD-NT to unmask the Cys192 residue to promote oxidation-mediated oligomerization and pyroptosis. Perturbation of either palmitoylation or depalmitoylation suppresses pyroptosis, extends the survival of mice from LPS-induced lethal septic shock and sensitizes mice to bacterial infection. Thus. our findings reveal a model through which a palmitoylation-depalmitoylationrelay spatially and temporally controls GSDMD activation in pyroptosis.
2024-02-25 | GSE252911 | GEO
Project description:Gasdermin D (GSDMD) is the executioner of pyroptosis, which is important for host defense against pathogen infection. After activation, caspase-mediated cleavage of GSDMD liberates an N-terminal fragment (GSDMD-NT), which oligomerizes and forms pores in the plasma membrane, leading to cell death and subsequent release of proinflammatory cytokines. How this process is spatiotemporally controlled to promote pyroptosis in cells has been a fundamental, unaddressed question. Here, we identify GSDMD as a substrate for reversible S-palmitoylation on cysteine 192 (Cys192) in response to lipopolysaccharide (LPS) stimulation. We found that the palmitoyl acyltransferase DHHC7palmitoylates GSDMD to direct its cleavage by caspases in pyroptosis by promoting the interaction of GSDMD and caspases. We further show that after GSDMD cleavage, palmitoylation of GSDMD-NTpromotes its plasma membrane translocation and binding, and then acyl protein thioesterase 2 (APT2) depalmitoylates GSDMD-NT to unmask the Cys192 residue to promote oxidation-mediated oligomerization and pyroptosis. Perturbation of either palmitoylation or depalmitoylation suppresses pyroptosis, extends the survival of mice from LPS-induced lethal septic shock and sensitizes mice to bacterial infection. Thus. our findings reveal a model through which a palmitoylation-depalmitoylationrelay spatially and temporally controls GSDMD activation in pyroptosis.
2024-02-25 | GSE252893 | GEO
Project description:Macrophages are involved in the pathophysiology of many diseases as critical cells of the innate immune system. Pyroptosis is a form of macrophage death that induces cytokinesis of phagocytic substances in the macrophages, thereby defending against infection. Dimethyl itaconate (DI) is an analog of itaconic acid with anti-inflammatory effects. However, the effect of dimethyl itaconate on macrophage pyroptosis has not been elucidated clearly. Thus, the present study aimed to analyze the effect of DI treatment on a macrophage pyroptosis model (Lipopolysaccharide, LPS+Adenosine Triphosphate, ATP). The results showed that 0.25 mM DI ameliorated macrophage pyroptosis and downregulated interleukin (IL)-1β expression. Then, real-time quantitative polymerase chain reaction (RT-qPCR) was used to confirm the result of RNA-sequencing of the upregulated oxidative stress-related genes (Gclc and Gss) and downregulated inflammation-related genes (IL-12β and IL-1β). In addition, Gene Ontology (GO) enrichment analysis showed that differential genes were associated with transcript levels and DNA replication. Kyoto encyclopedia of genes and genomes (KEGG) enrichment showed that signaling pathways, such as tumor necrosis factor (TNF), Jak, Toll-like receptor and IL-17, were altered after DI treatment. N-acetyl-L-cysteine (NAC) reversed the DI effect on the LPS+ATP-induced macrophage pyroptosis and upregulated the IL-1β expression. Oxidative stress-related protein Nrf2 is involved in the DI regulation of macrophage pyroptosis. Taken together, these findings suggested that DI alleviates the pyroptosis of macrophages through oxidative stress.
2021-10-16 | GSE185895 | GEO
Project description:The gram-negative bacterium lipopolysaccharide (LPS) is frequently administered to generate models of systemic inflammation. In particular, both kidney and lung are more sensitive to acute injury caused by LPS-induced systemic inflammation. However, there are several side effects and no effective treatment for LPS-induced systemic inflammation. PEGylated PDZ peptide was based on the first PDZ domain of the zonula occludens-1 (ZO-1) protein. PEGylated PDZ peptide was analyzed for effects on systemic inflammation induced by LPS. PDZ peptide administration led to restoration of tissue injuries (kidney, liver, and lung) and prevented alterations in biochemical plasma markers. The production of pro-inflammatory cytokines was significantly decreased in the plasma and lung BALF in the PDZ-administered mice. Flow cytometry analysis revealed the PDZ peptide significantly inhibited inflammation, mainly by decreasing the population of M1 macrophages, neutrophils (immature and mature), and increasing M2 macrophages. Using RNA sequencing analysis, the expression levels of the NF-κB-related proteins were lower in PDZ-treated cells than in LPS-treated cells. In addition, wild-type PDZ peptide significantly increased mitochondrial membrane integrity and decreased LPS-induced mitochondria fission. Interestingly, PDZ peptide dramatically could reduce LPS-induced NF-κB signaling, ROS production, and the expression of M1 macrophage marker proteins, but increased the expression of M2 macrophage marker proteins. These results indicated that PEGylated PDZ peptide inhibits LPS-induced systemic inflammation, reducing tissue injuries and reestablishing homeostasis and may be a therapeutic candidate against systemic inflammation.
2024-09-15 | GSE275635 | GEO