Transcriptional profile of LPS-stimulated murine macrophages treated with bacterially derived fatty acid
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE125930 | GEO | 2019/02/01
REPOSITORIES: GEO
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Project description:Transcriptional profile of LPS-stimulated murine macrophages treated with bacterially derived fatty acid
| PRJNA518018 | ENA
Project description:BACKGROUND: Dietary ABA-supplementation modulates immune and inflammatory responses in mouse models of chronic and infectious disease. However, the underlying mechanisms by which ABA elicits its immune modulatory effects are not well understood. This project used a systems approach in combination with functional and in vivo studies to investigate the target gene pathways modulated by ABA in the context of an inflammatory LPS challenge. RESULTS: Dietary ABA-supplementation regulates the expression of gene pathways associated with peroxisome proliferator-activated receptor gamma (PPAR g), cAMP signaling and lipid metabolism in PPAR g-expressing mice. However, the pattern of differentially expressed genes is significantly reduced in the spleens of tissue-specific PPAR g null mice fed ABA. These differences in gene expression coincided with enhanced PPAR g-reporter activity of macrophages treated with ABA and enhanced intracellular cAMP accumulation in ABA-treated splenocytes. Splenocytes from wild-type (WT) and Null (epithelial and immune cell-specific PPARg knock-out) mice were sampled with or without ABA supplementation and with or without LPS stimulation.
2010-09-01 | E-GEOD-21013 | biostudies-arrayexpress
Project description:The goal of this study was to compare the transcriptional responses of mouse macrophages treated with unsaturated or saturated fatty acids to macrophages treated with LPS to stimulate classical inflammatory activation. Microarray profiling was performed on total RNA isolated from primary mouse bone marrow-derived macrophages (BMDMs) treated with fatty acids (C18:1 oleic acid or C18:0 stearic acid), BSA vehicle, or LPS at two time points.
2016-03-18 | GSE77104 | GEO
Project description:BACKGROUND: Dietary ABA-supplementation modulates immune and inflammatory responses in mouse models of chronic and infectious disease. However, the underlying mechanisms by which ABA elicits its immune modulatory effects are not well understood. This project used a systems approach in combination with functional and in vivo studies to investigate the target gene pathways modulated by ABA in the context of an inflammatory LPS challenge. RESULTS: Dietary ABA-supplementation regulates the expression of gene pathways associated with peroxisome proliferator-activated receptor gamma (PPAR g), cAMP signaling and lipid metabolism in PPAR g-expressing mice. However, the pattern of differentially expressed genes is significantly reduced in the spleens of tissue-specific PPAR g null mice fed ABA. These differences in gene expression coincided with enhanced PPAR g-reporter activity of macrophages treated with ABA and enhanced intracellular cAMP accumulation in ABA-treated splenocytes.
2010-09-01 | GSE21013 | GEO
Project description:2,4-dinitrotoluene (2,4-DNT), a nitroaromatic used in industrial and explosive manufacturing processes, is known to contaminate artillery ranges, demilitarization areas and munitions manufacturing facilities. Previous transcriptomic and lipidomic studies identified energy metabolism as a principle biochemical process affected by 2,4-DNT where up-stream effects on PPAR? signaling were hypothesized as themolecular initiating event for these effects. Here, the validity of this hypothetical adverse outcome pathway (AOP) was assessed by testing the hypothesis that 2,4-DNT-induced perturbations in PPAR? signaling and resultant downstream deficits in energy metabolism, especially from lipids, would result in organism-level impacts on exercise endurance. PPAR? knock-out (-/-) and wild-type (WT) mice were exposed for 14 days to vehicle or 2,4-DNT at a dose (134 mg/kg/day) that did not exhibit overt systemic toxicity. Mice performed an exercise challenge (forced swim) 1 day after the last dose. 2,4-DNT decreased swim times in WT and PPAR? (-/-) mice, but the effect was significantly less in PPAR? (-/-) mice indicating the critical of PPAR? in mediating 2,4-DNT-induced energy metabolism deficits. 2,4-DNT caused down-regulation of transcripts involved in fatty acid metabolism, gluconeogenesis, triacylglycerol catabolism, and the pentose phosphate pathway, and 2,4-DNT treated wild-type mice had decreased serum trigylcerides and increased serum glucose versus 2,4-DNT treated PPAR? (-/-) mice. Our results support the hypothesis that 2,4-DNT perturbs PPAR? signaling as a molecular initiating event therefore impacting energy metabolism, especially lipid metabolism, producing reduced exercise endurance in mice. RNA was isolated from liver tissue of vehicle or 2,4-DNT treated wild-type or PPAR? (-/-) mice (n=6) and RT-PCR performed to analyze genes involved in fatty acid metabolism
2014-06-30 | E-GEOD-50168 | biostudies-arrayexpress
Project description:Hepatic metabolic derangements are key components in the development of fatty liver, insulin resistance, and atherosclerosis. SIRT1, a NAD+-dependent protein deacetylase, is an important regulator of energy homeostasis in response to nutrient availability. Here we demonstrate that hepatic SIRT1 regulates fatty acid metabolism by positively regulating PPAR-alpha. Hepatocyte-specific deletion of SIRT1 impairs PPAR-alpha signaling and decreased fatty acid beta-oxidation in the liver. When challenged with a high-fat diet, liver-specific SIRT1 knockout mice develop hepatic steatosis, hepatic inflammation, and endoplasmic reticulum stress. Taken together, our data indicate that SIRT1 plays a vital role in the regulation of hepatic lipid homeostasis.
2009-04-07 | GSE14921 | GEO
Project description:Dendritic cells (DCs) are the most potent antigen-presenting cells that play an important role in the crosstalk between the innate and the adaptive immune response. We identified quercetin exposure as an effective strategy to suppress DCs inflammatory response induced by LPS. In this study, using NGS analysis, we examined the effect of quercetin on miRNAs expression in DCs. We defined a signature of 113 miRNAs differentially regulated in LPS-stimulated DCs after quercetin exposure. Among them, we observed an upregulation of miR-369-3p that potentially regulated C/EBP-beta. We functionally demonstrate that the loss of function of miR-369-3p in LPS-stimulated DCs during quercetin exposure led to an increase of C/EBP-beta and its downstream targets TNFα and IL6. Conversely, we showed that the ectopic induction of miR-369-3p even without quercetin suppresses the inflammatory response of LPS reducing C/EBP-beta, TNFα and IL6 production. In vivo, oral administration of quercetin induces miR-369-3p expression. These data demonstrate that a key mediator of immunosuppressive effect of quercetin is miR-369-3p. These findings could have potentially therapeutic implications since the induction of miR-369-3p expression may have anti-inflammatory effect.
2019-12-31 | GSE112327 | GEO
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: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.
2012-03-07 | GSE32324 | GEO
Project description:The peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate glucose and lipid homeostasis. Activation of PPARs has been explored for the treatment of type 2 diabetes and dyslipidemia. LDT409 is a novel fatty acid like compound that has been shown to be a pan-active PPAR agonist. This data explores the changes in the liver proteome of mice treated with LDT409 while fed either a chow or high fat diet.
2024-05-22 | PXD047662 | Pride