The goal of the study was to identify the effects of TGF-beta on primary human macrophages maturated under different conditions.
Activation of a TGF-beta-specific multistep gene expression program in mature macrophages requires glucocorticoid-mediated surface expression of TGF-beta receptor II.
No sample metadata fields
View SamplesLymph node vs. tonsil
Differential expression of a gene signature for scavenger/lectin receptors by endothelial cells and macrophages in human lymph node sinuses, the primary sites of regional metastasis.
No sample metadata fields
View SamplesCarbon monoxide (CO) abrogates TNF-alpha mediated inflammatory responses in endothelial cells, yet, the underlying mechanism hereof is still elusive. We sought to explore potential mechanisms by which CO down-regulates VCAM-1 expression on TNF-alpha stimulated human umbilical vein endothelial cells (HUVEC). By genome-wide gene expression profiling and pathway analysis we studied the relevance of particular pathways for the anti-inflammatory effect of CO. In CO-releasing molecules-3 (CORM-3) stimulated HUVEC, significant changes in gene expression were found for genes implicated in the proteasome and porphyrine pathways. Although proteasome activities were increased by CORM-3, proteasome inhibitors did not abolish CORM-3s effect. Likewise, HO-1 inhibitors did not abrogate the ability of CORM-3 to down-regulate VCAM-1 expression. MAPK p38 was inhibited by CORM-3. Accordingly, VCAM-1 expression was down-regulated by the p38 inhibitor SB203580. Down-regulation of VCAM-1 by CORM-3 only occurred at concentrations that partly inhibit ATP production. Sodium azide and oligomycin paralleled the effect of CORM-3 in this regard. In conclusion, down-regulation of VCAM-1 by CORM-3 seems to be mediated via inhibition of p38 and mitochondrial respiration. Although CORM-3 up-regulates several genes in the ubiquitin proteasome sytem (UPS) or porphyrin pathway, there is no evidence that these changes are involved in the anti-inflammatory properties of CORM-3.
No associated publication
Cell line, Treatment
View SamplesProfiling CD34+ BCR-ABL+ cells of CML patients in chronic phase or blast crisis to identify differentially expressed stage-specific genes.
Gene expression profiling of CD34+ cells identifies a molecular signature of chronic myeloid leukemia blast crisis.
Sex, Age, Specimen part, Disease, Disease stage
View Samplesprofiling gene transcription in a mouse model of permanent focal cerebral ischemia that was induced by middle cerebral artery occlusion (MCAO)
Discovery of transcriptional programs in cerebral ischemia by in silico promoter analysis
Specimen part, Treatment, Time
View SamplesAlzheimer's disease (AD) is characterized by massive neurodegeneration and multiple changes in cellular processes, including neurogenesis. Proteolytic processing of the amyloid precursor protein (APP) plays a central role in AD. Due to varying APP processing, several beta-amyloid peptides are generated. In contrast to the form with 40 amino acids, the variant with 42 amino acids is thought to be the pathogenic form triggering the pathophysiological cascade in AD. Here, we studied the transcriptomic response to increased or decreased Abeta42 levels generated in human neuroblastoma cells. Genome-wide expression profiles (Affymetrix)were used to analyze the cellular response to the changed Abeta42 and Abeta40-levels. <br></br><br></br>Human neuroblastoma cell line SH-SY5Y is a thrice cloned (SK-N-SH -> SH-SY -> SH-SY5 -> SH-SY5Y) subline of the neuroblastoma cell line SK-N-SH which was isolated and established in 1970. This cell line has 47 chromosomes. The cells possess a unique marker comprised of a chromosome 1 with a complex insertion of an additional copy of a 1q segment into the long arm, resulting in trisomy of 1q. The cell lines used in this study are SHSY5Y transfected with the constructs pCEP-C99I45F, pCEP-C99V50F, pCEP-C99 wildtype or mock transfected with an empty vector. Independent cell clones of each transfected line were used to provide biological replicates.<br></br> Overexpressed C99 I45F is intracellularly cleaved resulting in high Abeta42, but low Abeta40 levels.<br></br> Overexpressed C99V50F is intracellularly cleaved resulting in low Abeta42, but high Abeta40 levels.<br></br>Overexpressed C99 wildtype is intracellularly cleaved resulting in medium Abeta42 and Abeta40 levels<br></br>Mock is the SHSY5Y cell line transfected with the empty vector pCEP (Invitrogen) as a negative control
New Alzheimer amyloid beta responsive genes identified in human neuroblastoma cells by hierarchical clustering.
Cell line, Subject
View SamplesCalyx of Held giant presynaptic terminals in the medial nucleus of the trapezoid body of the auditory brainstem form axosomatic synapses that have advanced to one of the best-studied synaptic system of the mammalian brain. As the auditory system matures and adjusts to high fidelity synaptic transmission, the calyx undergoes extensive structural and functional changes: it is formed around postnatal day 3 (P3), achieves immature function until hearing onset around P10 and can be considered mature from P21 onwards. This setting provides the unique opportunity to examine the repertoire of genes driving synaptic structure and function.
Gene expression profile during functional maturation of a central mammalian synapse.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Alteration of mRNA and microRNA expression profiles in rat muscular type vasculature in early postnatal development.
Sex
View SamplesFailures to produce neutralizing antibodies upon HIV-1 infection result in part from B cell dysfunction due to unspecific B cell activation. How HIV-1 affects antigen-specific B cell functions remains elusive. Using an adoptive transfer mouse model and ex vivo HIV infection of human tonsil tissue we found that expression of the HIV-1 pathogenesis factor NEF in CD4 T cells undermines their helper function and impairs cognate B cell functions including mounting of efficient specific IgG responses. NEF interfered with T cell help via a specific protein interaction motif that prevents polarized cytokine secretion at the T cell - B cell immune synapse. This interference reduced B cell activation and proliferation and thus disrupted germinal center formation and affinity maturation. These results identify NEF as a key component for HIV-mediated dysfunction of antigen-specific B cells. Therapeutic targeting of the identified molecular surface in NEF will facilitate host control of HIV infection.
HIV-1 infection of CD4 T cells impairs antigen-specific B cell function.
Specimen part
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