Dengue fever is an important tropical illness for which there is currently no virus-specific treatment. To shed light on mechanisms involved in the cellular response to dengue virus (DV), we assessed gene expression changes, using Affymetrix GeneChips (HG-U133A), of infected primary human cells and identified changes common to all cells. The common response genes included a set of 23 genes significantly induced upon DV infection of human umbilical vein endothelial cells (HUVECs), dendritic cells (DCs), monocytes, and B cells (analysis of variance, P < 0.05). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), one of the common response genes, was identified as a key link between type I and type II interferon response genes. We found that DV induces TRAIL expression in immune cells and HUVECs at the mRNA and protein levels. The induction of TRAIL expression by DV was found to be dependent on an intact type I interferon signaling pathway. A significant increase in DV RNA accumulation was observed in anti-TRAIL antibody-treated monocytes, B cells, and HUVECs, and, conversely, a decrease in DV RNA was seen in recombinant TRAIL-treated monocytes. Furthermore, recombinant TRAIL inhibited DV titers in DV-infected DCs by an apoptosis-independent mechanism. These data suggest that TRAIL plays an important role in the antiviral response to DV infection and is a candidate for antiviral interventions against DV.
TRAIL is a novel antiviral protein against dengue virus.
No sample metadata fields
View SamplesHutchinsonGilford progeria syndrome (HGPS) is a rare genetic disease with widespread phenotypic features resembling premature aging. HGPS was recently shown to be caused by dominant mutations in the LMNA gene, resulting in the in-frame deletion of 50 amino acids near the carboxyl terminus of the encoded lamin A protein. Children with this disease typically succumb to myocardial infarction or stroke caused by severe atherosclerosis at an average age of 13 years. To elucidate further the molecular
Genome-scale expression profiling of Hutchinson-Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelerated atherosclerosis.
Cell line
View SamplesGene expression profiling of murine irf4-/- and irf4+/+ splenic B cells identifies genes regulated by the transcription factor IRF4 in CD40+IL-4 activated mature B cells.
Asymmetric PI3K Signaling Driving Developmental and Regenerative Cell Fate Bifurcation.
Specimen part, Treatment
View SamplesOur goal was to demonstrate the similarity between the original keratinocytes and iPSC-derived keratinocytes from the same individual
Induced pluripotent stem cells from human revertant keratinocytes for the treatment of epidermolysis bullosa.
Specimen part
View SamplesThe effect of benzene exposure on peripheral blood mononuclear cell (PBMC) gene expression was examined in a population of shoe-factory workers with well-characterized occupational exposures to benzene.
Changes in the peripheral blood transcriptome associated with occupational benzene exposure identified by cross-comparison on two microarray platforms.
No sample metadata fields
View SamplesHuman toxicogenomic studies to date have been of limited size, have mainly addressed exposures at the upper end of typical ranges of human exposure, and have often lacked precise, individual estimates of exposure. Previously, we identified genes associated with exposure to high (>10 ppm) levels of the leukemogen, benzene, through transcriptomic analyses of blood cells from small numbers of occupationally exposed workers. Here, we have expanded the study to 125 workers exposed to a wide range of benzene levels, including <1 ppm. Study design, and analysis with a mixed effects model, removed sources of biological and experimental variability and revealed highly significant widespread perturbation of gene expression at all exposure levels. Benzene is an established cause of acute myeloid leukemia (AML), and may cause one or more lymphoid malignancies in humans. Interestingly, acute myeloid leukemia was among the most significant pathways impacted by benzene exposure in the present study. Further, at most exposure levels, immune response pathways including T cell receptor signaling, B cell receptor signaling, and Toll like receptor signaling were impacted, providing support for the biological plausibility of an association between lymphoma and benzene exposure. We also identified a 16-gene expression signature modified by all levels of benzene exposure, comprising genes with roles in immune response, inflammatory response, cell adhesion, cell-matrix adhesion, and blood coagulation. Overall, these findings support, and expand upon, our current understanding of the mechanisms by which benzene may induce hematotoxicity, leukemia and lymphoma. Furthermore, this study shows that with good study design and analysis, transcriptome profiling of the blood of chemically-exposed humans can identify relevant biomarkers across a range of exposures and inform about potential associations with disease risks.
Global gene expression profiling of a population exposed to a range of benzene levels.
Sex, Age, Subject
View SamplesExposure to indoor air pollution generated from the combustion of solid fuels is a major risk factor for a spectrum of cardiovascular and respiratory diseases, including lung cancer. In Chinas rural counties of Xuanwei and Fuyuan, lung cancer rates are among the highest in the country. While the elevated disease risk in this population has been linked to the widespread usage of bituminous (smoky) coal as compared to anthracite (smokeless) coal, the underlying physiologic mechanism that smoky coal induces in comparison to other fuel types is unclear. As we have previously used airway gene-expression profiling to gain molecular insights into the physiologic effects of cigarette smoke, here we profiled the buccal epithelium of residents exposed to the burning of smoky and smokeless coal in order to understand the physiologic effects of solid fuels.
Gene-expression profiling of buccal epithelium among non-smoking women exposed to household air pollution from smoky coal.
Sex, Age, Specimen part
View SamplesOur goal was to identify gene expression patterns that correlated with prevention of autoimmune alopecia in C3H/HeJ mice following alopecic graft transplantation
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Specimen part, Treatment
View SamplesOur goal was to identify gene expression patterns that correlated with treatment of established autoimmune alopecia in C3H/HeJ mice following alopecic graft transplantation
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Specimen part, Treatment
View SamplesOur goal was to develop a transcriptomic description of affected alopecic scalp skin from patients with alopecia areata.
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Specimen part
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