AhR activation by TCDD in the ET, cortical epithelial cell line
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE10168 | GEO | 2008/12/31
SECONDARY ACCESSION(S): PRJNA108369
REPOSITORIES: GEO
Similar Datasets
Project description:Over activation of the aryl hydrocarbon receptor (AhR) by TCDD results ampng other phenotypes in severe thymic atrophy accompanied by immunosuppression. The link between thymic atrophy, skewed thymocyte differntiation and immunosuppression is still not fully resolved. This study investigates the TCDD elicted exprssion changes in the ET, cortical thymus epithelial cell line. Keywords: TCDD, AhR, thymic epithelial cells, thymic involution, thymus atrophy ET cells were grown to 80-90% confluence and treated with 5nM TCDD or solvent control (1,4-Dioxane, 0,05%V). 2h,4h and 6h after treatment, RNA was isolated using TRIzol and gene expression measured. All experiments wer done in biological duplicates.
2008-12-30 | E-GEOD-10168 | 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: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
2008-11-25 | GSE10166 | GEO
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
2008-11-25 | GSE10084 | GEO
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:The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is regulated by environmental toxicants that function as AHR agonists such as 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). L-Type Amino Acid Transporter 1 (LAT1) is a leucine uptake transporter that is overexpressed in cancer. The regulation of LAT1 by AHR in MCF-7 and MDA-MB-231 breast cancer cells (BCCs) was investigated in this report. Ingenuity pathway analysis (IPA) revealed a significant association between TCDD-regulated genes (TRGs) and molecular transport. Overlapping the TCDD-RNA-Seq dataset in this report with a published TCDD-ChIP-seq dataset identified that LAT1 was a direct TCDD/AHR gene target. Short interfering RNA (siRNA)-directed knockdown of AHR confirmed that TCDD-stimulated increases in LAT1 mRNA and protein required AHR. TCDD-stimulated increases in LAT1 mRNA was also inhibited by the AHR antagonist CH-223191. Upregulation of LAT1 by TCDD coincided with increases in leucine uptake by MCF-7 cells in response to TCDD. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) assays revealed increases in AHR, AHR nuclear translocator (ARNT) and p300 binding and histone H3 acetylation at an AHR binding site in the LAT1 gene in response to TCDD. In MDA-MB-231 cells, which exhibit high levels of endogenous AHR activity, the levels of endogenous LAT1 mRNA and protein were reduced in response to knockdown of AHR with AHR-siRNA. The regulation of LAT1 by AHR stimulated MDA-MB-231 proliferation. Collectively, these findings have provided a deeper mechanistic understanding of extrinsic and intrinsic regulation of LAT1 by AHR.
2016-05-26 | GSE76608 | GEO
Project description:The thymus is one of the most affected organs during malnutrition, exhibiting atrophy and thymocyte depletion, characteristics that are also observed in several infectious diseases. The detrimental effects of malnutrition on immune responses to pathogens have long been recognized and it is considered a main risk factor for various infectious diseases, including visceral leishmaniasis (VL). However, the thymus has been barely studied during malnutrition and Leishmania infantum infection association. Protein malnutrition modifies intrathymic communication in L. infantum infected BALB/c mice by altering the abundance of proteins secreted to the thymic interstitial fluid (IF). We identified and compared protein abundance in the thymic IF samples from BALB/c mice that were fed with control protein (14%, CP) or low protein (4%, LP) isocaloric diets, followed by infection with L. infantum. By means of a quantitative proteomics approach using iTRAQ we identified 280 proteins of which 81% were reported as secreted by exosomes and 42% were previously described as secreted by thymic epithelial cells. LP-infected (LPi) animals showed a significant decrease in exosomal proteins, suggesting that exosomal carrier system is dysregulated in malnourished animals. LPi mice also exhibited an increase in the relative abundance of proteins involved in lipid metabolism and tricarboxylic acid cycle, suggestive of a non-proliferative microenvironment. Accordingly, flow cytometry analysis revealed that protein malnutrition decreases the proliferation of single positive and double positive T cells. Proteins engaged in glycolysis, protein ubiquitination and mRNA processing were significantly decreased. In addition, a significant decrease in the abundance of galectin-1 and increase of plasminogen were observed in malnourished animals. Together, the reduced cortical area, decreased proliferation, increased abundance of lipid- and tricarboxylic acid cycle-related proteins, and altered abundance of galectin-1 and plasminogen indicate a dysfunctional thymic microenvironment, where T cell migration, proliferation and maturation are compromised, contributing for the thymic atrophy observed in malnourished animals. All these alterations affect the control of the local and systemic infection, resulting in an impaired response to L. infantum infection.
2019-11-12 | PXD010414 | Pride
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: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 (Ahr–/–) 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 Ahr–/– 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. Keywords: treatment-control and mutant-wildtype
2008-11-01 | GSE10082 | GEO
Project description:TCDD do not activate AHR signaling in rat TS cells but do so in human TS cells with different biological outcomes. TCDD activates AHR signaling, stimulates the synthesis of 2 methoxy estradiol (2ME), a biologically active catechol estrogen, without directly affecting human TS cell differentiation. TCDD actions on human TS cells were dependent upon AHR signaling.
2024-10-08 | GSE246512 | GEO