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SRP118694
Homo sapiens
12 Downloadable Samples
Description
Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components. In this study, we apply epigenomic and transcriptomic analysis to a clinical trial of BCG vaccination in healthy adults. Overall design: Healthy volunteers were injected with the BCG vaccine, and monocytes were collected before vaccination, and 1 month after vaccination.
Publication Title
The role of Toll-like receptor 10 in modulation of trained immunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 43 Downloadable Samples
- NextSeq 500
Description
Metformin, the most widely administered diabetes drug, has been proposed as a candidate for host directed therapy for tuberculosis although very little is known about its effects on human host responses to Mycobacterium tuberculosis. When added in vitro to PBMCs isolated from healthy non-diabetic volunteers, metformin increased glycolysis, inhibited the mTOR targets, strongly reduced M. tuberculosis induced production of TNF-alpha (-58%), IFN-gamma (-47%) and IL-beta (-20%), while increasing phagocytosis. In healthy subjects, in vivo metformin intake induced significant transcriptional changes in whole blood and isolated PBMCs, with substantial down-regulation of genes related to inflammation and the type 1 interferon response. Metformin intake also increased monocyte phagocytosis (by 1.5 to 2 fold) and ROS production (+20%). These results show that metformin in humans has a range of potentially beneficial effects on cellular metabolism, immune function and gene-transcriptional level, that affect innate host responses to M. tuberculosis. This underlines the importance of cellular metabolism for host immunity and supports a role for metformin as host-directed therapy for tuberculosis. Overall design: Peripheral Mononuclear Cells taken from 11 healthy donors, prior to administration of metformin and after 5 days of metformin. Samples were stimulated with Mycobacterium tuberculosis lysate or cultured unstimulated for 4 hours. Total 88 samples, with 11 clinical replicates.
Publication Title
Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- NextSeq 500
Description
Metformin, the most widely administered diabetes drug, has been proposed as a candidate for host directed therapy for tuberculosis although very little is known about its effects on human host responses to Mycobacterium tuberculosis. When added in vitro to PBMCs isolated from healthy non-diabetic volunteers, metformin increased glycolysis, inhibited the mTOR targets, strongly reduced M. tuberculosis induced production of TNF-a (-58%), IFN-gamma (-47%) and IL-1ß (-20%), while increasing phagocytosis. In healthy subjects, in vivo metformin intake induced significant transcriptional changes in whole blood and isolated PBMCs, with substantial down-regulation of genes related to inflammation and the type 1 interferon response. Metformin intake also increased monocyte phagocytosis (by 1.5 to 2 fold) and ROS production (+20%). These results show that metformin in humans has a range of potentially beneficial effects on cellular metabolism, immune function and gene-transcriptional level, that affect innate host responses to M. tuberculosis. This underlines the importance of cellular metabolism for host immunity and supports a role for metformin as host-directed therapy for tuberculosis. Overall design: Ex vivo blood RNA samples analyzed from 11 healthy donors, prior to administration of metformin (control) and after 5 days of metformin (test). Total 22 samples, with 11 clinical replicates.
Publication Title
Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
CD8+ T cells are pre-programmed for cytotoxic differentiation. However, a subset of effector CD8+ T cells (Tc17) produce IL-17 and fail to express cytotoxic genes. Here, we show that the transcription factors directing IL-17 production inhibit cytotoxicity despite persistent Runx3 expression. Cytotoxic gene repression did not require the transcription factor Thpok. We further show that STAT3 restrained cytotoxic gene expression in CD8+ T cells and that RORgt represses cytotoxic genes by inhibiting the functions but not the expression of the cytotoxic transcription factors T-bet and Eomesodermin. Thus, the transcriptional circuitry directing IL-17 expression inhibits cytotoxic functions.
Publication Title
A STAT3-dependent transcriptional circuitry inhibits cytotoxic gene expression in T cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
CD8+ T cells are pre-programmed for cytotoxic differentiation. However, a subset of effector CD8+ T cells (Tc17) produce IL-17 and fail to express cytotoxic genes. Here, we show that the transcription factors directing IL-17 production inhibit cytotoxicity despite persistent Runx3 expression. Cytotoxic gene repression did not require the transcription factor Thpok. We further show that STAT3 restrained cytotoxic gene expression in CD8+ T cells and that RORgt represses cytotoxic genes by inhibiting the functions but not the expression of the cytotoxic transcription factors T-bet and Eomesodermin. Thus, the transcriptional circuitry directing IL-17 expression inhibits cytotoxic functions.
Publication Title
A STAT3-dependent transcriptional circuitry inhibits cytotoxic gene expression in T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PI3K/AKT pathway plays one of pivotal roles in breast cancer development and maintenance. PIK3CA, coding PIK3 catalytic subunit, is the oncogene which shows the high frequency of gain-of-function mutations leading to the PI3K/AKT pathway activation in breast cancer. In particular in the ER-positive breast tumors PIK3CA mutations have been observed in 30% to 40%. However, genes expressed in connection to the pathway activation in breast tumorigenesis remain largely unknown.
Publication Title
Gene expression profiling reveals new aspects of PIK3CA mutation in ERalpha-positive breast cancer: major implication of the Wnt signaling pathway.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Morphogenesis of the mammary gland relies on the precise developmental control of morphological elements including TEBs, ducts and lobules. In the peripubertal mammary gland, rising levels of ovarian hormones control this development through a tightly controlled genetic program where specific sets of genes are up-regulated.
Publication Title
In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Extracellular-regulated kinases (ERK1/2 and 5) are known to play important roles in growth and drug resistance of various cancers. Here we show roles of inhibition of ERK1, ERK2, or ERK5 on gene expression profiles of epithelioid malignant mesothelioma (MM) cells (HMESO).
Publication Title
Blocking of ERK1 and ERK2 sensitizes human mesothelioma cells to doxorubicin.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 57 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human mesothelial cells (LP9/TERT-1) were exposed to low and high (15 and 75 m2/cm2 dish) equal surface area concentrations of crocidolite asbestos, nonfibrous talc, fine titanium dioxide (TiO2), or glass beads for 8 or 24 h. RNA was then isolated for Affymetrix microarrays, GeneSifter analysis and QRT-PCR. Gene changes by asbestos were concentration- and time-dependent. At low nontoxic concentrations, asbestos caused significant changes in mRNA expression of 29 genes at 8 h and 205 genes at 24 h, whereas changes in mRNA levels of 236 genes occurred in cells exposed to high concentrations of asbestos for 8 h. Human primary pleural mesothelial cells also showed the same patterns of increased gene expression by asbestos. Nonfibrous talc at low concentrations in LP9/TERT-1 mesothelial cells caused increased expression of 1 gene Activating Transcription Factor 3 (ATF3) at 8 h and no changes at 24 h, whereas expression levels of 30 genes were elevated at 8 h at high talc concentrations. Fine TiO2 or glass beads caused no changes in gene expression. In human ovarian epithelial (IOSE) cells, asbestos at high concentrations elevated expression of 2 genes (NR4A2, MIP2) at 8 h and 16 genes at 24 h that were distinct from those elevated in mesothelial cells. Since ATF3 was the most highly expressed gene by asbestos, its functional importance in cytokine production by LP9/TERT-1 cells was assessed using siRNA approaches. Results reveal that ATF3 modulates production of inflammatory cytokines (IL-1, IL-13, G-CSF) and growth factors (VEGF and PDGF-BB) in human mesothelial cells.
Publication Title
Alterations in gene expression in human mesothelial cells correlate with mineral pathogenicity.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Vascular endothelial growth factor is a multifunctional cytokine playing important roles in angiogenesis, tumor progression and metastasis. Alternative splicing results in the production of several different isoforms of VEGF. We have previously generated human breast cancer cells overexpressing VEGF165 or VEGF189 isoforms (referred to as the V165 and V189 clones, respectively) and showed that VEGF189-transfected cells were less tumorigenic. In this study, we used bioluminescence imaging to analyze the metastasis capacity of breast cancer cell lines (MDA-MB-321) overexpressing VEGF isoforms in nude mice. V165, V189 and control cV clones were transfected with a luciferase plasmid to generate bioluminescent clones (the V165-B, V189-B and cV clones, respectively). These clones were then injected into the left heart ventricle of nude mice.
Publication Title
MDA-MB-231 breast cancer cells overexpressing single VEGF isoforms display distinct colonisation characteristics.
Sample Metadata Fields
No sample metadata fields
View Samples