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: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. 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: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:Controlled decay of cytokine and chemokine mRNAs restrains the time and amplitude of inflammatory responses. Tristetraprolin (TTP) binds to AU-rich elements in 3´ untranslated regions of mRNA and targets the bound mRNA for degradation. We have addressed here the function of TTP in balancing the macrophage activation state by a comprehensive analysis of TTP-dependent mRNA decay in LPS-stimulated macrophages from WT and TTP-deficient mice. We compared mRNA stability in LPS-treated BMDMs from WT and TTP-/- mice by microarray-based measurement of the remnant mRNA after transcriptional blockade with actinomycin D (act D). To increase the sensitivity of the mRNA decay profiling we inhibited the LPS-activated p38 MAPK with the specific inhibitor SB203580 since p38 MAPK negatively regulates the mRNA-destabilizing activity of TTP. LPS stimulation was for 3h before addition of act D. RNA was harvested at 0', 45' and 90' thereafter.
2011-12-15 | E-GEOD-28880 | biostudies-arrayexpress
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:Controlled decay of cytokine and chemokine mRNAs restrains the time and amplitude of inflammatory responses. Tristetraprolin (TTP) binds to AU-rich elements in 3´ untranslated regions of mRNA and targets the bound mRNA for degradation. We have addressed here the function of TTP in balancing the macrophage activation state by a comprehensive analysis of TTP-dependent mRNA decay in LPS-stimulated macrophages from WT and TTP-deficient mice.
2011-12-15 | GSE28880 | GEO
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.
2019-05-15 | E-MTAB-6064 | biostudies-arrayexpress
Project description:The inflammatory response initiated by microbial products signaling through Toll-like receptors (TLRs) of the innate immune system is essential for host defense against infection. Because inflammation can be harmful to host tissues, the innate response is highly regulated. Negative regulation of TLR4, the receptor for bacterial lipopolysaccharide (LPS), results in LPS tolerance, defined as hyporesponsiveness to repeated stimulation with LPS. LPS tolerance is thought to protect the host from excessive inflammation by turning off TLR4 signal, which then shuts down TLR-induced genes. However, TLR signaling induces hundreds of genes with very different functions. We reasoned that genes with different functions should have different requirements for regulation. Specifically, genes encoding proinflammatory mediators should be transiently inactivated to limit tissue damage, while genes encoding antimicrobial effectors, which directly target pathogens, should remain inducible in tolerant cells to protect the host from infection. Using an in vitro system of LPS tolerance in macrophages, here we show that TLR-induced genes may indeed be divided into two distinct categories based on their functions and regulatory requirements. Further, we show these distinct groups are regulated by gene-specific, and not signal-specific mechanisms. Keywords: Treatment Comparison
2007-04-22 | GSE7348 | GEO