Transcription profiling of mouse Primary Langerhans cells in animals treated with TCDD
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Charlotte Esser
PROVIDER: E-GEOD-9506 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The arylhydrocarbon receptor is a ligand inducible transcription factor. Known to control xenobiotic metabolizing enzymes, it also affects - depending on the cell type - numerous other genes, either directly or indirectly. With respect to the immune system, persistent activation leads to immunosuppression. We asked how the AhR is involved in Langerhans cells. These antigen presenting cells of the skin are responsible for allergies against chemicals (thus xenobiotic metabolism might be relevant) and a recently detected endogenous ligand, FICZ made by UVB radiation from tryptophane, is particularly abundant in the skin. Experiment Overall Design: ear skin epidermal sheets from AhR exon2 deficient mice and wildtype C57BL/6 mice were isolated and cultivated for 16 hours in standard medium. Tissues were then homogenized and Langerhans cells isolated via BSA gradient and cell sorting to greater 95% purity. RNA was preparedand amplified prior to chip-hybridization using the MessageAmp⢠Kit of Ambion (Woodward St. Austin, USA). RNA was biotinylated (Enzo Bio Arrayâ¢HighYield⢠RNA transcript labeling kit (Affymetrix, High Wycombe, UK)) and purified. RNA was hybridized to MOE430A gene chips (Affymetrix).
2009-11-16 | E-GEOD-13130 | biostudies-arrayexpress
Project description:Over-activation of the aryl hydrocarbon receptor by TCDD in mice leads among other phenotypes to a severe thymic atrophy accompanied by immunosuppression. TCDD causes a block in thymocyte maturation and a preferential emigration of immature CD4-CD8- DN thymocytes (recent thymic emigrants) into the periphery. As part of this study gene expression profiles from DN thymocytes and thymic emigrants were generated from TCDD and solvent control mice Keywords: Affymetrix, TCDD, CD4-CD8- thymocytes, Thymus involution, thymic emigration, Ahr Female, 6-8 week old C57BL6 mice were i.p. injected with 10 M-BM-5g/kg TCDD. After 5 days mice were anesthezised and FITC injected into their thymi. after 24h mice were sacrificed and CD4-CD8-FITC+ cells isolated from thymus (thymocytes) and spleen (recent thymus emigrants).
2008-11-25 | E-GEOD-10166 | biostudies-arrayexpress
Project description:CD4+ T cells from 8-12 week female mice were isolated from wt and AhR-/- mice 24h after injection of 10µg/kg TCDD or solvent control. Keywords: TCDD, AHR, immunosuppression Each experiment was performed in biological duplicates from 4 pooled animals. Since TCDD treatment showed only marginal impact on the gene expression (~10 transcripts effected in wt mice) wt - ko comparisons were performed on pooled profiles from TCDD and solvent mice.
2008-11-25 | E-GEOD-10084 | biostudies-arrayexpress
Project description:We propose a novel method of generating Langehans cell in culture. This sequencing dataset was produced in order to confirm the authenticity of the monocyte-derived LC produced in culture.
2019-11-27 | GSE141048 | GEO
Project description:The transcriptome of murine LC after 24 hours in vivo exposure to a moderate dose of 10 microgram 2,3,7,8-tetrachlorodibenzo-p-dioxin was studied. It was found that mice, although they express the arylhydrocarbon receptor abundantly in LC, are inert to its activation. Target genes are not inducible, in contrast to many other cell types. Keywords: toxic effect, single dose
2009-05-01 | GSE9506 | GEO
Project description:The cardioprotective effects of long chain (LC) 3PUFA can be achieved at the gene expression level, notably in liver. However, the complexity of biological pathways modulations and the nature of the bioactive molecules are still under investigation. The present study aimed to investigate the dose-response effects of LC 3PUFA on the production of peroxidated metabolites and on global gene expression in liver. The intake of LC ?3PUFA increased, in a dose-dependent manner, their incorporation in liver phospholipids but also the hepatic production of 4-HHE. Pathways related to inflammation were dose-dependently associated with the 3 groups but Group 2 was rather associated with inflammatory effects while Group 3 was anti-inflammatory. LC ?3PUFA had no effect on PPAR-controlled genes. However, they modified, in a dose-dependent manner, the expression of major genes related to lipoprotein metabolism (LDLR, VLDLR, INSIG1 and MTTP), possibly through the FXR signaling pathway. In conclusion, the effect of LC ?3PUFA is dependent on the dose possibly because of the production of peroxidated metabolites such as 4-HHE. New-Zealand white rabbits were fed (7 wk) a high cholesterol diet and received by daily oral gavages either oleic acid rich oil or a mixture of oils providing 0.1% (Group 1), 0.5% (Group 2) or 1% (Group 3) of energy as docosahexaenoic acid. Specific peroxidated metabolite issued from LC 3PUFA (4-hydroxyhexenal or 4-HHE) were measured by GC/MS/MS and transcription profiling was conducted in liver. Differentially expressed genes were identified using Bioconductor (Moderated p<0.05, Fold Change>1.20) and clustered into pathways (Ingenuity Pathway Analysis 7.0).
2011-06-04 | E-GEOD-27621 | biostudies-arrayexpress
Project description:The aryl hydrocarbon receptor (AHR) is a widely-expressed ligand-dependent transcription-factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Indeed, AHR-null mice are refractory to the physiological effects of dioxin-exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue-specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. Previously we employed studied the transcriptional responses of wild-type and AHR-null C57BL/6J mice to dioxin-exposure. We found that essentially all hepatic effects of dioxin were mediated by the AHR, and that large numbers of genes were affected by dioxin exposure. Surprisingly, we also identified a large effect of AHR genotype, even in the absence of dioxin-exposure. To help assess the tissue-specificity of AHR activity we replicated that prior study in the kidney from the same animals previously studied, and extensively compared the hepatic and renal transcriptional profiles. We find that dioxin-exposure causes essentially no transcriptional effects in the absence of a functional AHR in either liver or kidney. Surprisingly, aside from a number of well-established AHR target genes, dioxin-exposure has few effects in animals harbouring a wild-type AHR. By contrast, AHR genotype profoundly remodels the renal transcriptome, and is associated with perturbation of specific functional pathways and with specific DNA motifs. Our results demonstrate the importance of inter-tissue comparisons and highlight the basal role of AHR activity in renal and hepatic development or normal physiology. Two-Factor, Two-Level. AHRnull and wildtype mice were treated with dioxin (TCDD) or corn oil vehicle. 3 replicates per treatment for AHRnull mice, 6 replicates of dioxin treatment for wildtype mice, and 5 replicates of corn oil treatment for wildtype mice.
2009-09-21 | E-GEOD-15858 | biostudies-arrayexpress
Project description:Conventional biochemical and molecular techniques identified previously several genes whose expression is regulated by the aryl hydrocarbon receptor (AHR). We sought to map the complete spectrum of AHR-dependent genes in male adult liver using expression arrays to contrast mRNA profiles in Ahr-null mice (Ahrâ/â) with those in mice with wild-type AHR (Ahr+/+). Transcript profiles were determined both in untreated mice and in mice treated 19 h earlier with 1000 µg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Expression of 456 ProbeSets was significantly altered by TCDD in an AHR-dependent manner, including members of the classic AHRE-I gene battery, such as Cyp1a1, Cyp1a2, Cyp1b1, and Nqo1. In the absence of exogenous ligand, AHR status alone affected expression of 392 ProbeSets, suggesting that the AHR has multiple functions in normal physiology. In Ahrâ/â mice, only 32 ProbeSets exhibited responses to TCDD, indicating that the AHR is required for virtually all transcriptional responses to dioxin exposure in liver. The flavin-containing monooxygenases, Fmo2 and Fmo3, considered previously to be uninducible, were highly induced by TCDD in an AHR-dependent manner. The estrogen receptor alpha as well as two estrogen-receptor-related genes (alpha and gamma) exhibit AHR-dependent expression, thereby extending cross-talk opportunities between the intensively studied AHR and estrogen receptor pathways. p53 binding sites are over-represented in genes down-regulated by TCDD, suggesting that TCDD inhibits p53 transcriptional activity. Overall, our study identifies a wide range of genes that depend on the AHR, either for constitutive expression or for response to TCDD. Experiment Overall Design: Mice bearing wild-type or genetically deleted AHRs were treated with corn oil vehicle or TCDD, and their livers analyzed by expression arrays.
2008-11-13 | E-GEOD-10082 | biostudies-arrayexpress
Project description:The aryl hydrocarbon receptor (AHR) is a widely-expressed ligand-dependent transcription-factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Indeed, AHR-null mice are refractory to the physiological effects of dioxin-exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue-specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. Previously we employed studied the transcriptional responses of wild-type and AHR-null C57BL/6J mice to dioxin-exposure. We found that essentially all hepatic effects of dioxin were mediated by the AHR, and that large numbers of genes were affected by dioxin exposure. Surprisingly, we also identified a large effect of AHR genotype, even in the absence of dioxin-exposure. To help assess the tissue-specificity of AHR activity we replicated that prior study in the kidney from the same animals previously studied, and extensively compared the hepatic and renal transcriptional profiles. We find that dioxin-exposure causes essentially no transcriptional effects in the absence of a functional AHR in either liver or kidney. Surprisingly, aside from a number of well-established AHR target genes, dioxin-exposure has few effects in animals harbouring a wild-type AHR. By contrast, AHR genotype profoundly remodels the renal transcriptome, and is associated with perturbation of specific functional pathways and with specific DNA motifs. Our results demonstrate the importance of inter-tissue comparisons and highlight the basal role of AHR activity in renal and hepatic development or normal physiology. Two-Factor, Two-Level. AHRnull and wildtype mice were treated with dioxin (TCDD) or corn oil vehicle. 3 replicates per treatment for AHRnull mice, and 6 replicates per treatment for wildtype mice.
2009-09-21 | E-GEOD-15857 | biostudies-arrayexpress
Project description:Background; Mouse and rat models are mainstays in pharmacology, toxicology and drug development â?? but differences between strains and between species complicate data interpretation and application to human health. Dioxin-like polyhalogenated aromatic hydrocarbons represent a major class of environmentally and economically relevant toxicants. In mammals dioxin exposure leads to a broad spectrum of adverse affects, including hepatotoxicity of varying severity. Several studies have shown that dioxins extensively alter hepatic mRNA levels. Surprisingly, though, analysis of a limited portion of the transcriptome revealed that rat and mouse responses diverge greatly (Boverhof et al. Toxicol Sci 94:398â??416, 2006). Results; We employed oligonucleotide arrays to compare the response of 8,125 rat and mouse orthologs. We confirmed that there is limited inter-species overlap in dioxin-responsive genes. Rat-specific and mouse-specific genes are enriched for specific functional groups which differ between species, conceivably accounting for species-specificities in liver histopathology. While no evidence for the involvement of copy-number variation was found, extensive inter-species variation in the transcriptional-regulatory network was identified; Nr2f1 and Fos emerged as candidates to explain species-specific and species-independent responses, respectively. Conclusion; Our results suggest that a small core of genes is responsible for mediating the similar features of dioxin hepatotoxicity in rats and mice but non-overlapping pathways are simultaneously at play to result in distinctive histopathological outcomes. The extreme divergence between mouse and rat transcriptomic responses appears to reflect divergent transcriptional-regulatory networks. Taken together, these data suggest that both rat and mouse models should be used to screen the acute hepatotoxic effects of drugs and toxic compounds. Experiment Overall Design: Wild-type C57BL/6 mice were treated with 1000 ug/kg TCDD (n=6) or with cornoil vehicle as control (n=5) for 19 hours. Their livers were then excised, RNA extracted, and the resulting samples hybridized to Affymetrix MOE430-2 arrays to survey changes in the transcriptome profile.
2008-10-26 | E-GEOD-10769 | biostudies-arrayexpress