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GSE112229
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The major surface glycoprotein (Msg) is the most abundant surface protein of Pneumocystis species. Given that Msg is present on both the cyst and trophic form of Pneumocystis, and dendritic cells play a critical role in initiating host immune responses, we undertook studies to examine activation of bone marrow-derived myeloid dendritic cells by Msg purified from P. murina. Incubation of dendritic cells with Msg did not lead to increased expression of CD40, CD80, CD86, or MHCII, or increased secretion of any of 10 cytokines. Microarray analysis identified very few differentially expressed genes. In contrast, LPS activated dendritic cells by all of these assays. However, Msg did bind to mouse mannose macrophage receptor and human DC-SIGN, two C-type lectins expressed by dendritic cells that are important in recognition of pathogen-associated high mannose glycoproteins. Deglycosylation of Msg demonstrated that this binding was dependent on glycosylation. These studies suggest that Pneumocystis has developed a mechanism to avoid activation of dendritic cells, potentially by the previously identified loss of genes that are responsible for the high level of protein mannosylation found in other fungi.
Publication Title
The Major Surface Glycoprotein of Pneumocystis murina Does Not Activate Dendritic Cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Interleukin-6 (IL-6) is an important growth factor for estrogen receptor-alpha (ER) positive breast cancer, and elevated serum IL-6 is associated with poor prognosis. We firstly demonstrated that pSTAT3 is the primary downstream IL-6 signaling pathway in ER-positive breast cancer, using ten different breast cancer cell lines. Three-dimensional cultures of these cell lines were also used to develop a 17-gene IL-6 specific gene signature that could be used to identify IL-6 driven disease. This signature included a variety of genes involved in immune cell function and migration, cell growth and apoptosis, and the tumor microenvironment. To further validate this IL-6 signature, we obtained 36 human ER-positive breast cancer tumor samples with matched serum for gene expression profiling and determination of an IL-6 pathway activation score (PAS). Patients with high IL-6 PAS were also enriched for elevated serum IL-6 (>=10 pg/ml). We then utilized a murine MCF-7 xenograft model to determine the role of IL-6 in ER-positive breast cancer and potential anti-IL-6 therapy in vivo. When IL-6 was administered in vivo, MCF-7 cells engrafted without the need for estrogen supplementation. Subsequently, we prophylactically treated mice at MCF-7 engraftment with an anti-IL-6 antibody (siltuximab), fulvestrant or combination therapy. Siltuximab alone was able to blunt MCF-7 engraftment. Similarly, when tumors were allowed to grow to 125 mm3 before treatment, siltuximab alone demonstrated tumor regressions in 90% (9/10) of tumors. Given the established role for IL-6 in ER+ breast cancer, this data demonstrates the potential for anti-IL-6 therapeutics.
Publication Title
Interleukin-6 is a potential therapeutic target in interleukin-6 dependent, estrogen receptor-α-positive breast cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
For both CD4 and micropajfe cell types, upregulated genes were primarily related to immune activation and proliferation, while down-regulated genes represented more diverse processes, including cell membranes, vasculature development, cell adhesion, and lipid-related metabolic processes.
Publication Title
Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
For both CD4 and micropajfe cell types, upregulated genes were primarily related to immune activation and proliferation, while down-regulated genes represented more diverse processes, including cell membranes, vasculature development, cell adhesion, and lipid-related metabolic processes.
Publication Title
Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In wild-type mice, expression of chemokines that are ligands for Ccr2, Cxcr3, and Cxcr2 increased at days 32 to 41 post-infection, with a return to baseline by day 75. Concomitant increases were seen in Ccr2 and Cxcr3 but not in Cxcr2 expression. Induction of these same factors also occurred in CD40-ligand and CD40 knockout mice but only at a much later time-point, during uncontrolled Pneumocystis pneumonia (PCP). Expression of CD4 Th1 markers was increased in wild-type mice during clearance of infection. Ccr2 and Cx3cr1 knockout mice cleared Pneumocystis infection with kinetics similar to wild-type mice, and all animals developed anti-Pneumocystis antibodies. Upregulation of Ccr2 and Cxcr3 and their ligands supports an important role for T helper cells and mononuclear phagocytes in the clearance of Pneumocystis infection. However, based on the current and prior studies, no single chemokine receptor appears to be critical to the clearance of Pneumocystis.
Publication Title
Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We found that a H3K4 specific histone methyltransferase MLL1, a mammalian homologue of Drosophila trithorax, is essential for circadian transcription. MLL1 is in a complex with CLOCK:BMAL1 and contributes to their rhythmic recruitment to circadian promoters and cyclic H3K4 tri-metylation. To analyze the function of MLL1 on circadian gene regulation, we performed comparative microarray analysis of global gene expression levels in WT and MLL1-deficient MEF, at two different circadian time points (CT18 and CT30). This analysis identified several genes whose expression levels were remarkably changed between CT18 and CT30 in WT and MLL1-KO MEF. Typical clock-regulated genes such as Per2, Per3, Bmal1, or Dbp were found to be changing in WT but not in MLL1-KO MEFs.
Publication Title
The histone methyltransferase MLL1 permits the oscillation of circadian gene expression.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis. In the current study we examined whether -1,3 glucans are masked by surface proteins in Pneumocystis, and what role -glucans play in Pneumocystis-associated inflammation. For 3 species, including P. jirovecii, which causes Pneumocystis pneumonia (PCP) in humans, P. carinii, and P. murina, -1,3 glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment. Using Q-PCR and microarray techniques, we demonstrated in a mouse model of PCP that treatment with caspofungin, an inhibitor of -1,3 glucan synthesis, for 21 days, decreased expression of a broad panel of inflammatory markers, including IFN-, TNF-, IL-1, IL-6, and multiple chemokines/chemokine ligands. Thus, -glucans in Pneumocystis cysts are largely masked, which likely decreases innate immune activation; this mechanism presumably was developed for interactions with immunocompetent hosts, in whom organism loads are substantially lower. In immunosuppressed hosts with a high organism burden, organism death and release of glucans appears to be an important contributor to deleterious host inflammatory responses.
Publication Title
β-Glucans Are Masked but Contribute to Pulmonary Inflammation During Pneumocystis Pneumonia.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Prostate cancer (PCa) development and progression are associated with chronic inflammation. The cytokine interleukin (IL)-6 can influence progression, differentiation, survival, and angiogenesis of PCa. To identify novel pathways that are triggered by IL-6, we performed a gene expression profiling of two PCa cell lines, LNCaP and MDA PCa 2b, under treatment with 5 ng/ml IL-6. Interferon regulatory factor (IRF)9 was identified as one of the most prevalent IL-6 regulated genes in both cell lines. IRF9 is a mediator of type I interferon signaling and acts together with signal transduction and activator of transcription (STAT)1 and 2 to activate transcription of interferon responsive genes. The IL-6 regulation of IRF9 was confirmed at mRNA and protein levels by quantitative real-time PCR and Western blot, respectively, in both cell lines and could be blocked by the anti-IL-6 antibody Siltuximab. Three PCa cell lines with an autocrine IL-6 loop, PC3, DU145, and LNCaP-IL-6+, showed a high expression of IRF9. A tissue microarray with 36 malignant and adjacent 36 benign areas from prostate cancer specimens showed that IRF9 protein expression is moderately elevated in malignant areas and positively correlates with the tissue expression of IL-6. Downregulation and overexpression of IRF9 provided evidence for an interferon-independent role of IRF9 on cellular proliferation of different PCa cell lines. Furthermore, expression of IRF9 was essential to mediate the antiproliferative effects of IFN-2. We concluded that IL-6 is an inducer of IRF9 expression in prostate cancer and a sensitizer for the antiproliferative effects of IFN2.
Publication Title
IL6 sensitizes prostate cancer to the antiproliferative effect of IFNα2 through IRF9.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mouse and human stem cells with features similar to those of embryonic stem cells have been derived from testicular cells. Although pluripotent stem cells have been obtained from defined germline stem cells (GSCs) of mouse neonatal testis, only multipotent stem cells have been obtained so far from defined cells of mouse adult testis. In this study we describe a robust and reproducible protocol for obtaining germline-derived pluripotent stem (gPS) cells from adult unipotent GSCs. Pluripotency of gPS cells was confirmed by in vitro and in vivo differentiation, including germ cell contribution and transmission. As determined by clonal analyses, gPS cells indeed originate from unipotent GSCs. We propose that the conversion process requires a GSC culture microenvironment that depends on the initial number of plated GSCs and the length of culture time.
Publication Title
Induction of pluripotency in adult unipotent germline stem cells.
Sample Metadata Fields
No sample metadata fields
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