Extrarenal viral infections commonly trigger glomerulonephritis mostly in association with immune complex disease. The immunoglobulin component of immune complexes can activate glomerular cell Fc receptors but whether complexed viral nucleic acids contribute to glomerular inflammation remains unknown. Glomerular mesangial cells express TLR3 but lack TLR7-9, hence, it is unclear whether mesangial cells can recognize and respond to viral ssRNA or DNA. Here we studied the immune responses activated by 3P-RNA (5'Triphosphate RNA) and Non-CpG DNA (Double stranded DNA) in primary mesangial cells (PMC).
Viral RNA and DNA trigger common antiviral responses in mesangial cells.
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View SamplesTissue inhibitor of metalloproteinase 1 (TIMP-1) controls matrix metalloproteinase (MMP) activity through 1:1 stochiometric binding. Human TIMP-1 fused to a glycosylphosphatidylinositol (GPI) anchor (TIMP-1-GPI) shifts the activity of TIMP-1 from the extracellular matrix to the cell surface. TIMP-1-GPI treated renal cell carcinoma cells (RCC) show increased apoptosis and reduced proliferation. Transcriptomic profiling and regulatory pathway mapping were used to identify potential mechanisms driving these effects. Significant changes in inhibitor of DNA binding (IDs), TGF-1/SMAD and BMP pathways resulted from TIMP-1-GPI treatment. These events were linked to reduced TGF-1 signaling mediated by inhibition of proteolytic processing of latent TGF-1 by TIMP-1-GPI.
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Specimen part
View SamplesPurpose: ASA404 (Vadimezan) belongs to a class of agents with disrupting properties against tumor vasculature, which is partly mediated by TNF-signaling. Our aim was to investigate the potential therapeutic applicability of ASA404 against endocrine tumors. Experimental Design: We determined anti-tumoral effects in preclinical models of neuroendocrine tumors of the gastroenteropancreatic system [1] and adrenocortical cancer (NCI-H295R) by histology and immunohistochemistry. Furthermore, we characterized these models with their clearly different responsiveness regarding TNF synthesis and signaling. Results: Upon treatment of tumor bearing mice significant anti-tumoral effects, an increase in TNF as well as TNF-specific activation of downstream signaling were evident in the BON tumor model while no comparable effects were detectable for NCI-H295R. Two important modulator of TNF-signaling, toll-like-receptor 4 (TLR-4) and its adaptor protein LY96 were found highly expressed in BON tumors and transgenic expression in NCI-H295R partly restored TNF responsiveness. Furthermore, expression of IRAK2-kinase, which has recently been linked to TLR-4-signaling as a mediator of sustained TNF release was induced upon TNF-treatment in BON, but not in NCI-H295R cells. Finally, we identified TNFAIP3/A20, a member of an inhibitory feedback-loop downstream of both investigated signaling cascades, as overexpressed in the adrenocortical carcinoma tumor model. Subsequent analyses of clinical patient samples confirmed a correlation between tumor TNFAIP3 expression levels and overall survival in patients with ACC. Conclusions: Taken together our findings provide evidence that modulation of TNF-signaling could be of relevance both for the clinical course of ACC patients and as a marker of treatment response.
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Specimen part, Treatment
View SamplesThe specific contribution of the two TNF-receptors Tnfr1 and Tnfr2 to TNF-induced inflammation in the glomerulus is unknown. In mice, TNF exposure induces glomerular expression of inflammatory mediators like adhesion molecules and chemokines in vivo, and glomerular accumulation of leukocytes.
Distinct contributions of TNF receptor 1 and 2 to TNF-induced glomerular inflammation in mice.
Specimen part, Treatment
View SamplesFoxp1 is expressed throughout B cell development, but the physiological functions in mature B lymphocytes are unknown. We therefore evaluated differential gene expression in Foxp1-deficient B cells, with or
Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells.
Specimen part
View SamplesOncogene-induced senescence in early mPanIN lesions depends on intact RelA function in vivo. We investigated the difference in gene expression between KrasG12D pancreata with and without deletion of RelA. Pancreata from 7 day old mice were prepared, RNA was isolated and Affymetrix microarray expression analysis was performed.
No associated publication
Age, Specimen part
View SamplesExamination of gene expression patterns in lineage negative FLT3-ITD and pMIG-transduced BM cells via microarray study.
RIPK3 Restricts Myeloid Leukemogenesis by Promoting Cell Death and Differentiation of Leukemia Initiating Cells.
Specimen part
View SamplesLBH589 is a histone deacetylase (HDAC) inhibitor, treatment and changes in acetylated histones alters gene expression
Pan-histone deacetylase inhibitor panobinostat sensitizes gastric cancer cells to anthracyclines via induction of CITED2.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part
View SamplesReveal differentially regulated genes and cellular pathways within allergic and non-allergic asthmatic children compared to healthy controls
No associated publication
Specimen part
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