Recognition and response to gram-positive bacteria by macrophages and dendritic cells is mediated in part through TLR2. We found that that Streptococcus pneumoniae cell wall fragments, containing primarily peptidoglycan and teichoic acids, induced prodigious secretion of IL-10 from macrophages and dendritic cells and was dependent on TLR2 and NOD2, a cytoplasmic CARD-NACHT-LRR protein encoded by Card15. IL-10 secretion in response to cell walls was also dependent on RICK/RIP2, a kinase associated with NOD2, and MYD88 but independent of the ERK/p38 pathway. The reduction of IL-10 secretion by cell wall-activated NOD2-deficient myeloidderived cells translated into downstream effects on IL-10 target gene expression and elevations in subsets of pro-inflammatory cytokine expression normally restrained by autocrine/paracrine effects of IL-10. Since NOD2 is linked to aberrant immune responses in Crohns Disease patients bearing mutations in CARD15, the temporal and quantitative effects of the TLR2/NOD/RICK pathway on IL-10 secretion may affect homeostatic control of immune responses to gram-positive bacteria.
The TLR2-MyD88-NOD2-RIPK2 signalling axis regulates a balanced pro-inflammatory and IL-10-mediated anti-inflammatory cytokine response to Gram-positive cell walls.
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View SamplesWe perform microarray analysis of HUVECs upon stimulation with virulent wildtype C. albicans strain SC5314 or its efg1/efg1 cph1/cph1 hyphal-deficient derivative strain CAN34 to compare the gene expression profiles elicited from HUVECs in response to these strains. In addition, these responses are compared to that of TNF-alpha induced responses to determine which responses are Candida-specific.
Transcriptome profile of the vascular endothelial cell response to Candida albicans.
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Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes.
Specimen part
View SamplesSingle nucleotide polymorphisms (SNP) can affect mRNA gene expression, in a tissue-specific manner. In this work we survey association of SNP alleles with mRNA gene expression in human dorsal root ganglions (DRG) to gain insights into pathophysiology of pain phenotypes.
Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes.
Specimen part
View SamplesSingle nucleotide polymorphisms (SNP) can affect mRNA gene expression, in a tissue-specific manner. In this work we survey association of SNP alleles with mRNA gene expression in human dorsal root ganglions (DRG) to gain insights into pathophysiology of pain phenotypes.
Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes.
Specimen part
View SamplesAims/hypothesis Due to their ability to regulate various signalling pathways (cytokines, hormones, growth factors), the suppressor of cytokine signalling (SOCS) proteins are thought to be promising therapeutic targets for metabolic and inflammatory disorders. Hence, their role in vivo has to be precisely determined.
Constitutive expression of suppressor of cytokine signalling-3 in skeletal muscle leads to reduced mobility and overweight in mice.
Specimen part, Subject
View SamplesExtracorporeal photochemotherapy (ECP) is widely used to treat cutaneous T cell lymphoma, graft versus host disease and allografted organ rejection. Its clinical and experimental efficacy in both cancer immunotherapy and autoreactive disorders suggests a novel mechanism. This study reveals that ECP induces a high percentage of processed monocytes to enter the dendritic antigen presenting cell (DC) differentiation pathway, as determined by expression of relevant genes. The resulting DC are capable of processing and presentation of exogenous antigen and are largely maturationally synchronized, as assessed by the level of expression of co-stimulatory surface molecules. Principal component analysis of the ECP-induced monocyte transcriptome indicates that activation or suppression of more than 3500 genes produces a reproducible distinctive molecular signature. Pathway analysis suggests that DC maturation may be triggered by transient adherence of passaged monocytes to plasma proteins coating the ECP plastic ultraviolet exposure plate. Co-incubation with lymphocytes, simultaneously induced by ECP to undergo apoptosis, may accelerate conversion of monocytes to DC. The efficiency with which ECP induces new functional DC supports the possibility that these cells participate prominently in the clinical successes of the treatment. ECP may offer a practical source of DC for use in a spectrum of immunotherapeutic trials.
Rapid generation of maturationally synchronized human dendritic cells: contribution to the clinical efficacy of extracorporeal photochemotherapy.
Disease, Disease stage
View SamplesDouble-stranded RNA (dsRNA) can enter different pathways in mammalian cells, including sequence-specific RNA interference, sequence-independent interferon response and editing by adenosine deaminases. To assess the potential of expressed dsRNA to induce interferon stimulated genes in somatic cells, we performed microarray analysis of HEK293 and HeLa cells transfected with a MosIR plasmid expressing an mRNA with a long inverted repeat structure in its 3UTR (MosIR) or with a parental MosIR plasmid (without inverted repeat) as a control.
dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells.
Specimen part
View SamplesGene expression data was analyzed to map with urine proteomics data
Mining the human urine proteome for monitoring renal transplant injury.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mutation of senataxin alters disease-specific transcriptional networks in patients with ataxia with oculomotor apraxia type 2.
Disease
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