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.
Langerhans cell maturation and contact hypersensitivity are impaired in aryl hydrocarbon receptor-null mice.
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View SamplesThe 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.
Langerhans cell maturation and contact hypersensitivity are impaired in aryl hydrocarbon receptor-null mice.
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View SamplesTreatment of cancer cells with anti-cancer drugs often fails to achieve complete remission. Yet, such drug treatments may induce alteration in the tumor’s gene expression patterns, including those of Cancer/Testis Antigens (CTA). The degradation products of such antigens can be presented as HLA peptides on the surface of the tumor cells and be developed into anti-cancer immunotherapeutics. For example, the DNA methyl transferase inhibitor, 5-aza-2''-deoxycytidine (Decitabine) has limited anti-tumor efficacy, yet it induces the expression of many genes, including CTAs that are normally silenced in the healthy adult tissues. In this study, the presentation of many new HLA peptides derived from CTAs and induced by Decitabine was demonstrated in three human Glioblastoma cell lines. Such presentation of CTA-derived HLA peptides can be exploited for development of new treatment modalities, combining drug treatment with anti-CTA targeted immunotherapy. The Decitabine-induced HLA peptidomes include many CTAs that are not normally detected in healthy tissues or in cancer cells, unless treated with the drug. In addition, the study included large-scale analyses of the simultaneous effects of Decitabine on the transcriptomes, proteomes and HLA peptidomes of the human Glioblastoma cells. It demonstrates the poor correlations between these three levels of gene expression, both in their total levels and in their response to the drug. Overall design: The transcriptomes, proteomes and HLA peptidomes of the U-87, T98G and LNT-229 GBM human cell lines were analyzed before and after treatment with Decitabine. Overall, the RNA-Seq transcriptome analyses resulted in the identification of above 26000 transcripts, the proteome analyses identified about 7500 proteins and the HLA class I peptidome analyses resulted in above 25000 identified HLA peptides. Two biological repetitions of the transcriptome, three of the proteome and three of the HLA peptidome were performed with each of the cell lines and treatment, resulting in highly reproducible datasets.
Human Leukocyte Antigen (HLA) Peptides Derived from Tumor Antigens Induced by Inhibition of DNA Methylation for Development of Drug-facilitated Immunotherapy.
Specimen part, Cell line, Treatment, Subject
View SamplesIn the present study we investigate the role of IL-4 receptor a subunit in intestinal inflammation using DSS-induced colitis model. Our finding suggest that IL-4Ra deficiency enhances intestinal mucosal barrier function through the upregulation of NOX1-dependent ROS production, thereby suppressing the development of intestinal inflammation.
Interleukin-4 Receptor α Subunit Deficiency Alleviates Murine Intestinal Inflammation In Vivo Through the Enhancement of Intestinal Mucosal Barrier Function.
Sex, Specimen part, Treatment
View Samples[original Title] Comparison of expression data of primary murine melanocytes from aryl hydrocarbon deficient mice and corresponding wild-type C57BL/6 mice
The aryl hydrocarbon receptor mediates UVB radiation-induced skin tanning.
Sex, Specimen part
View SamplesShikonin is a active component isolated from the roots of the traditional Chinese herb Lithospermum erythrorhizon and exhibits multiple pharmacological properties, such as anti-oxidant, anti-inflammatory, and anti-tumor effects. Here, the effects of shikonin on the gene expression of human lymphoma U937 cells were investigated using an Affymetrix GeneChip system. The cells were treated with 100 nM shikonin, and followed by incubation for 3h at 37C. Flow cytometry analysis with Annexin-V and propidium iodide demonstrated that no cell death was observed in the cells at 100 nM shikonin. Of approximately 47,000 probe sets analyzed, many genes that were differentially expressed by a factor 2.0 or greater were identified in the cells treated with the compound.
Chemical inducers of heat shock proteins derived from medicinal plants and cytoprotective genes response.
Cell line, Treatment
View SamplesYoung individuals possess distinct properties that adults do not. The juvenile animals show higher activities for growth, healing, learning and plasticity than adults. The machinery for establishing these juvenile properties is not fully understood. To better understand the molecular constituents for the above properties, we performed a comprehensive transcriptome analysis of differently aged cells of mice by high-throughput sequencing. The samples are isolated mouse hepatocytes and caridomyocytes in triplicate. As a result, we identified the genes selectively highly expressed in the young cells. These genes, collectively called as juvenility-associated genes (JAGs), show significant enrichments in the functions such as alternative splicing, phosphorylation and extracellular matrix (ECM). This implies the juvenescence might be achieved by these functions at the cell level. The JAG mutations are associated with progeria syndromes and growth disorders. Thus, the JAGs might organize the juvenile property of young animals and analysis of JAGs may provide scientific and therapeutic approaches toward treating the genetic diseases.
Identification of juvenility-associated genes in the mouse hepatocytes and cardiomyocytes.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity.
Sex, Age, Specimen part
View SamplesWhite adipose tissue (WAT) is a highly active metabolic and endocrine organ, and its dysfunction links obesity to a variety of diseases, ranging from type 2 diabetes to cancer. The function of WAT is under the control of multiple cell signaling systems, including that of G protein-coupled receptors (GPCRs). Gs- and Gi-coupled receptors have been reported to regulate lipolysis, and Gq-coupled receptors stimulate glucose uptake in adipocytes. However, the roles of G12/13-coupled receptors in WAT are totally unknown. Here we show that lysophosphatidic acid receptor 4 (LPA4), an adipose cluster GPCR, selectively activates G12/13 proteins in adipocytes, and limits continuous remodeling and healthy expansion of WAT in mice. Under standard diet conditions, LPA4-knockout mice showed higher expression levels of mitochondrial biogenesis-related genes in WAT, along with higher production of adiponectin than control mice. In vitro studies have consistently demonstrated that the LPA4/Rho/Rho-kinase signaling pathway suppresses mRNA expression of mitochondrial biogenesis-related genes in adipocytes. In a diet-induced obesity model, LPA4-deficient mice showed metabolically healthy obese phenotypes, with continuous WAT expansion, and protection from WAT inflammation, hepatosteatosis, and insulin resistance. Given that GPCRs comprise the most successful class of drug targets, LPA4 would be a promising therapeutic target for obesity-related metabolic disorders.
The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity.
Sex, Age, Specimen part
View SamplesWhite adipose tissue (WAT) is a highly active metabolic and endocrine organ, and its dysfunction links obesity to a variety of diseases, ranging from type 2 diabetes to cancer. The function of WAT is under the control of multiple cell signaling systems, including that of G protein-coupled receptors (GPCRs). Gs- and Gi-coupled receptors have been reported to regulate lipolysis, and Gq-coupled receptors stimulate glucose uptake in adipocytes. However, the roles of G12/13-coupled receptors in WAT are totally unknown. Here we show that lysophosphatidic acid receptor 4 (LPA4), an adipose cluster GPCR, selectively activates G12/13 proteins in adipocytes, and limits continuous remodeling and healthy expansion of WAT in mice. Under standard diet conditions, LPA4-knockout mice showed higher expression levels of mitochondrial biogenesis-related genes in WAT, along with higher production of adiponectin than control mice. In vitro studies have consistently demonstrated that the LPA4/Rho/Rho-kinase signaling pathway suppresses mRNA expression of mitochondrial biogenesis-related genes in adipocytes. In a diet-induced obesity model, LPA4-deficient mice showed metabolically healthy obese phenotypes, with continuous WAT expansion, and protection from WAT inflammation, hepatosteatosis, and insulin resistance. Given that GPCRs comprise the most successful class of drug targets, LPA4 would be a promising therapeutic target for obesity-related metabolic disorders.
The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity.
Sex, Age, Specimen part
View Samples