Effects of high molecular weight phthalates on LPS-stimulated THP-1 macrophages - proteome
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: 
Isabel Karkossa
LAB HEAD: Kristin Schubert
PROVIDER: PXD043025 | Pride | 2023-09-13
REPOSITORIES: Pride
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Project description:In this study, the effects of three high molecular weight phthalates (DINP, DIDP, DPHP) and their metabolites (MHINP, MCINP, OHMPHP) were investigated in THP-1 macrophages. For this purpose, the redoxome, including overall as well as reversible cysteine oxidation, was evaluated.
2023-09-13 | PXD043139 | Pride
Project description:In this study, the effects of three high molecular weight phthalates (DINP, DIDP, DPHP) and their metabolites (MHINP, MCINP, OHMPHP) were investigated in THP-1 macrophages. For this purpose, the phosphoproteome was evaluated.
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Project description:In this study, the effects of Triclosan (TCS) and its alternatives, including Benzalkonium chloride (BAM), Benzethonium chloride (BEC), Chloroxylenol (CEO), Chlorhexidine (CHX) and Cetylpyridinium chloride (CPC), were investigated in THP-1 macrophages. For this purpose, untargeted proteomics was applied.
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Project description:Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS). To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches - gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq) analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac) and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII), which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of up-regulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF), was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines), was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40%) was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at the chromatin level for specific genes and this study highlights the level of fine-tuning that occurs in the immune response. 2 pairs of THP-1 cells either stimulated with LPS or not. ChIP using either H3K9/K14Ac, RNA Pol II (phospho S5) or SP1 antibody. This submission represents chip-seq component of study.
2012-03-07 | E-GEOD-32324 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE32141: Expression analysis LPS stimulated THP-1 cells in four paired samples GSE32324: ChIP-seq analysis LPS stimulated THP-1 cells Refer to individual Series
2012-03-07 | E-GEOD-32325 | biostudies-arrayexpress
Project description:Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS). To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches - gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq) analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac) and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII), which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of up-regulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF), was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines), was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40%) was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at the chromatin level for specific genes and this study highlights the level of fine-tuning that occurs in the immune response. 4 pairs of THP-1 cells either stimulated with LPS or not This submission represents transcriptome component of study.
2012-03-07 | E-GEOD-32141 | biostudies-arrayexpress
Project description:Inflammatory processes play an important role in regulation of ovarian development, in particularly early in life. Neonatal immune challenge by administration of lipopolysaccharide (LPS) has been previously demonstrated to result in diminished ovarian reserve and altered reproductive lifespan. In this study we aimed to characterise the cellular mechanisms that may underpin impaired ovulatory capacity and reduced oocyte development, induced by LPS treatment. Rat pups were administered with LPS or saline on postnatal days 3 and 5. Ovaries were obtained on postnatal day 7 to examine the effect of LPS administration on the ovarian transcriptome. Rat pups were administered intraperitoneally either 0.05mg/kg of LPS (Salmonella Enteritidis) or an equivalent volume of non-pyrogenic saline on postnatal days (PNDs) 3 and 5, and ovaries were obtained on PND 7 for RNA extraction and hybridization on an Agilent-028279 SurePrint G3 Rat GE 8x60K Array platform.
2013-04-27 | E-GEOD-46436 | biostudies-arrayexpress
Project description:Monocytes are key players in inflammatory processes which are triggered by lipopolysaccharide (LPS), the major outer membrane component of gram-negative bacteria. The present study in human monocytic THP-1 cells was designed in order to identify LPS-inducible genes which are down-regulated by the reduced form of CoQ10 (ubiquinol, Q10H2). For this purpose, THP-1 cells were incubated with 10 µM Q10H2 for 24 h. Subsequently, cells were stimulated for 4 h with 1µg/ml LPS and the resulting gene expression levels were determined using microarrays. 14 LPS-inducible genes were identified to be significantly (p < 0.05) down-regulated by Q10H2 pre-treatment between a factor of 1.32 and 1.65. The strongest effect of Q10H2 incubation was found for the nuclear receptor coactivator 2 gene (NCOA2). Gene Ontology (GO) terms revealed for the Q10H2-sensitive genes an involvement in e.g. signal transduction processes (CENTD1, NCOA2, PSD3, PPP2R5C), transcriptional regulation (NCOA2, POU2F1, ETV3) and cell proliferation pathways (CCDC100, EPS15). In conclusion, we provide evidence in THP-1 cells that the reduced form of CoQ10 (Q10H2) modulates LPS-induced gene expression. Whole genome expression profiles were analysed from monocytes pre-incubated with the reduced form of CoQ10 (ubiquinol, Q10H2) before subsequent stimulation with LPS. Stimulated (+LPS) and unstimulated (-LPS) monocytes were used as positive and negative controls, respectively. For every experimental group (3 groups in total), three Affymetrix Human Genome U133 Plus 2.0 arrays were used, thus resulting in the analysis of 9 microarrays.
2010-12-22 | E-GEOD-19627 | biostudies-arrayexpress
Project description:Coenzyme Q10 (CoQ10) is an obligatory element in the respiratory chain and functions as a potent antioxidant of lipid membranes. More recently, anti-inflammatory effects as well as an impact of CoQ10 on gene expression have been observed. To reveal putative effects of Q10 on LPS-induced gene expression, whole genome expression analysis was performed in the monocytic cell line THP-1. 1129 probe sets have been identified to be significantly up-regulated (p < 0.05) in LPS-treated cells when compared to controls. Text mining analysis of the top 50 LPS up-regulated genes revealed a functional connection in the NFκB pathway and confirmed our applied in vitro stimulation model. Moreover, 33 LPS-sensitive genes have been identified to be significantly down-regulated by Q10-treatment between a factor of 1.32 and 1.85. GeneOntology (GO) analysis revealed for the Q10-sensitve genes a primary involvement in protein metabolism, cell proliferation and transcriptional processes. Three genes were either related to NFκB transcription factor activity, cytokinesis or modulation of oxidative stress. In conclusion, our data provide evidence that Q10 down-regulates LPS-inducible genes in the monocytic cell line THP-1. Thus, the previously described effects of Q10 on the reduction of pro-inflammatory mediators might be due to its impact on gene expression. Whole genome expression profiles were analysed from monocytes pre-incubated with ubiquinone (Q10) before subsequent stimulation with LPS. Stimulated (+LPS) and unstimulated (-LPS) monocytes were used as positive and negative controls, respectively. For every experimental group (3 groups in total), three Affymetrix Human Genome U133 Plus 2.0 arrays were used, thus resulting in the analysis of 9 microarrays.
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Project description:In this study we performed an RNA-seq analysis of lipopolysaccharide (LPS) and palmitate (PAL) stimulated THP-1 macrophages to study the gene regulatory mechanisms underlying classical innnate immune response and chronical inflammatory response caused by metabolic stress. This analysis was done to complement single-cell transcriptome analyses of the same cell models.
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