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GSE41296
Homo sapiens
120 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression analysis has been established as a tool for the characterization of genotoxic mechanisms of chemical mutagens. This approach has been shown to differentiate between DNA reactive genotoxins and non-DNA reactive or indirectly-acting genotoxins. In this context, it has been suggested that expression analysis is capable of distinguishing compounds that cause DNA damage from those that interfere with mitotic spindle function. Formaldehyde (FA) is known to be a DNA-reactive substance which mainly induces chromosomal damage in cultured mammalian cells. However, there has been concern that FA might also act as an aneugen (i.e., induce aneuploidy) but recent cytogenetic studies did not support this assumption. To further characterize FA's genotoxic mode of action, we now used gene expression profiling as a molecular tool to differentiate between clastogenic and aneugenic activity. TK6 cells were exposed to FA for 4 and 24 h and changes in gene expression were analyzed using a whole-genome human microarray. Results were compared to the expression profiles of two DNA-damaging clastogens (methyl methanesulfonate [MMS] and ethyl methanesulfonate [EMS]) and two aneugens (colcemid [COL] and vincristine [VCR]). The gene expression profiles indicated that clastogens and aneugens induce discriminable gene expression patterns. The expression profile of FA showed more similarities to clastogens than to aneugens. Hierarchical clustering analysis as well as several class prediction algorithms revealed a much closer relationship of FA with clastogens than with aneugens. A pathway analysis of differentially regulated genes also demonstrated an overall better agreement of FA with clastogens than with aneugens. Altogether, the results of this study revealed great similarities in gene expression in response to FA and clastogens but did not support an aneugenic activity of FA.
Publication Title
Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Using various exposure conditions, we studied the induction of DNA-protein crosslinks (DPX) by formaldehyde (FA) and their removal in primary human nasal epithelial cells (HNEC). DPX were indirectly measured by the alkaline comet assay as the reduction of gamma ray induced DNA migration. DPX are the most relevant primary DNA alterations induced by FA and the comet assay is a very sensitive method for the detection of FA-induced DPX. In parallel experiments, we investigated changes in gene expression by using a full genome human microarray. After a single treatment with FA (50 to 200 M), concentration and time-dependent changes in gene expression were seen under conditions that also induced genotoxicity. Repeated treatments with low FA concentrations (20 and 50 M) did not lead to a significant induction of DPX but repeated treatments with 50 M FA changed the expression of more than 100 genes. Interestingly, the expression of genes involved in the main pathway for FA detoxification and the repair of DPX were not specifically enhanced. A high degree of overlap was seen among the pattern of gene changes induced by FA in HNEC in comparison to recently published array studies for nasal epithelial cells from rats exposed to FA in vivo. Our results suggest that HNEC are a suited in vitro model for the characterization of FA-induced toxicity and the relationship between genotoxic and other cytotoxic effects.
Publication Title
Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
TLRs are considered important for innate immune responses that combat bacterial infections. Here, the role of TLRs in severe septic peritonitis using the colon ascendens stent peritonitis (CASP) model was examined. We demonstrate that mice deficient for MyD88 and TRIF had markedly reduced bacterial numbers both in peritoneal cavity and peripheral blood, indicating that bacterial clearance in this model is inhibited by TLR signals. Moreover, survival of Myd88-/-;TrifLps2/Lps2 mice was significantly improved. The lack of TLR signals prevented the excessive induction of inflammatory cytokines and of IL 10. Notably, the expression of IFN-gamma, which has an essential protective role in septic peritonitis, and of IFN-regulated genes including several p47 and p65 GTPases as well as IP 10 was independent of TLR signaling. These results provide evidence that, in severe septic peritonitis, TLR deficiency balances the innate immune response in a favorable manner by attenuating deleterious responses such as excessive cytokine release, while leaving intact protective IFN-gamma production.
Publication Title
Improved host defense against septic peritonitis in mice lacking MyD88 and TRIF is linked to a normal interferon response.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The macrolide rapamycin is known for its immunosuppressive properties since it inhibits mTOR (mammalian target of rapamycin), which activity affects differentiation and functions of various innate and adaptive immune cells involved in graft-versus-host disease development. Since rapamycin procures immunosuppressive effects on the immune response, rapamycin is an attractive candidate for graft-versus-host disease prevention after allogeneic bone marrow transplantation
Publication Title
Rapamycin-based graft-versus-host disease prophylaxis increases the immunosuppressivity of myeloid-derived suppressor cells without affecting T cells and anti-tumor cytotoxicity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The macrolide rapamycin is known for its immunosuppressive properties since it inhibits mTOR (mammalian target of rapamycin), which activity affects differentiation and functions of various innate and adaptive immune cells involved in graft-versus-host disease development. Since rapamycin procures immunosuppressive effects on the immune response, rapamycin is an attractive candidate for graft-versus-host disease prevention after allogeneic bone marrow transplantation. Recently, an activating effect of rapamycin on the function of myeloid-derived suppressor cells (MDSCs), a subset of immune suppressive cells of myeloid origin was reported. However, the effect of rapamycin treatment on MDSCs induction and function in the management of graft-versus-host disease is largely unknown.
Publication Title
Rapamycin-based graft-versus-host disease prophylaxis increases the immunosuppressivity of myeloid-derived suppressor cells without affecting T cells and anti-tumor cytotoxicity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Long-term treatment of Kasumi-1 cells at clinically attained doses of dasatinib led to decreased drug-sensitivity by means of IC50 values (relative to treatment-naive cells). Changes were paralled by profound alterations in c-KIT expression and cell signaling signatures. Upon brief discontinuation of dasatinib treatment, these alterations reversed and drug sensitivity was restored.
Publication Title
Transitory dasatinib-resistant states in KIT(mut) t(8;21) acute myeloid leukemia cells correlate with altered KIT expression.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
CD69 is a transmembrane protein expressed on the surface of activated leukocyte. The ligand for CD69 and the intracellular signaling pathway of this molecule are yet unknown. It is widely used as a marker of activated lymphocyte, but its function in immune system is not known.
Publication Title
CD69 regulates type I IFN-induced tolerogenic signals to mucosal CD4 T cells that attenuate their colitogenic potential.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The anaphylatoxin C5a is a potent mediator of innate immunity and promotes inflammation via its receptor C5aR1 upon complement system activation danger-associated molecular patterns. Both C5a and C5aR1 are thought to be contributing factors in inflammatory and infectious conditions of the bone. Bone fracture healing, for example, was significantly improved when applying a C5aR1-antagonist in a rodent model of severe systemic inflammation and osteoblasts were found to be target cells for C5a in this setting. Interestingly, osteoblasts up-regulate C5aR1 during osteogenic differentiation and after bone injury. Further, C5a induces inflammatory cytokines, such as IL-6, and the osteoclastogenic mediator RANKL in osteoblasts. However, the molecular mechanisms underlying C5a-C5aR1 signaling axis in osteoblasts remain unclear, and further targets of C5a are still elusive. Using microarray analysis, we analyzed intracellular events following C5aR1 activation in osteoblasts and defined up- or down-regulated genes and their belonging biological pathways.
Publication Title
C5aR1 interacts with TLR2 in osteoblasts and stimulates the osteoclast-inducing chemokine CXCL10.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Large cell lymphomas of the gastrointestinal tract are currently regarded as diffuse large B-cell lymphomas despite a more favourable clinical outcome and a lower aggressiveness compared to other nodal and extranodal DLBCL. We compared gene expression profiles of 28 gastrointestinal marginal zone B-cell lymphomas and variants with several other B-cell lymphoma entities such as Burkitts lymphoma, nodal DLBCL, follicular lymphoma, mantle cell lymphoma, primary mediastinal B-cell lymphoma and normal B-cell populations. Based on a subset of NF-kappaB target genes, partitioning and hierarchical cluster algorithms were used which led to comparable results. The different B-cell subsets, the Burkitts lymphoma, and the small cell lymphomas formed distinct groups, respectively. The DLBCL were subdivided into one group containing only DLBCL samples, one subset clustered together with the PMBL samples, and another one together with the blastic variants of MZBL. These results implicate that extranodal blastic MZBL represent a distinct subgroup of DLBCL.
Publication Title
Comparative gene-expression profiling of the large cell variant of gastrointestinal marginal-zone B-cell lymphoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
41 volunteers (male non-smokers) were exposed to formaldehyde (FA) vapors for 4 h per day over a period of 5 working days under strictly controlled conditions. For each exposure day, different exposure concentrations were used in a random order ranging from 0 up to 0.7 ppm. At concentrations of 0.3 ppm and 0.4 ppm, four peaks of 0.6 or 0.8 ppm for 15 min each were applied. During exposure, subjects had to perform bicycle exercises (about 80 W) four times for 15 min. Blood samples, exfoliated nasal mucosa cells and nasal biopsies were taken before the first and after the last exposure. Nasal epithelial cells were additionally sampled 1, 2 and 3 weeks after the end of the exposure period. The alkaline comet assay, the sister chromatid exchange (SCE) test and the cytokinesis-block micronucleus test (CBMNT) were performed with blood samples. The micronucleus test (MNT) was also performed with exfoliated nasal mucosa cells. The expression (mRNA level) of the GSH-dependent formaldehyde dehydrogenase (FDH, identical to alcohol dehydrogenase 5; ADH5; EC 1.2.1.46) was measured in blood samples by quantitative real-time RT-PCR with TaqMan probes. DNA microarray analyses using a full-genome human microarray were performed on blood samples and nasal biopsies of selected subgroups with the highest FA exposure at different days. None of the tests performed showed a biologically significant effect related to FA exposure. Under the experimental conditions of this study, inhalation of FA did not lead to genotoxic effects in peripheral blood cells and nasal mucosa and had no effect on the expression of the FDH gene. Inhalation of FA also did not cause biologically relevant alterations in the expression of genes in a microarray analysis with nasal biopsies and peripheral blood cells.
Publication Title
Assessment of genotoxic effects and changes in gene expression in humans exposed to formaldehyde by inhalation under controlled conditions.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples