Search results for "Downregulation"
showing 10 items of 460 documents
The down-regulation of miR-125b in chronic lymphocytic leukemias leads to metabolic adaptation of cells to a transformed state
2012
AbstractMiR-125b-1 maps at 11q24, a chromosomal region close to the epicenter of 11q23 deletions in chronic lymphocytic leukemias (CLLs). Our results establish that both aggressive and indolent CLL patients show reduced expression of miR-125b. Overexpression of miR-125b in CLL-derived cell lines resulted in the repression of many transcripts encoding enzymes implicated in cell metabolism. Metabolomics analyses showed that miR-125b overexpression modulated glucose, glutathione, lipid, and glycerolipid metabolism. Changes on the same metabolic pathways also were observed in CLLs. We furthermore analyzed the expression of some of miR-125b–target transcripts that are potentially involved in the…
Altered expression of nonclassical HLA class Ib antigens in human renal cell carcinoma and its association with impaired immune response
2003
Abstract An optimal antitumoral immune response requires the activation of both CD8 + and CD4 + T lymphocytes by the peptide antigen presentation via the human leukocyte antigen (HLA) class I and class II molecules, respectively. Downregulation or loss of HLA molecules has been found in human renal cell carcinoma (RCC) and provides a strategy of these tumors to evade T-cell mediated immunosurveillance. In addition, a tumor-specific upregulation of HLA-G has been recently described in RCC, which also leads to an impaired immune response. We here summarize the frequency of the constitutive and/or interferon-γ (IFN-γ) inducible expression of nonclassical HLA class Ib antigens in RCC cell lines…
Obesity alters the gustatory perception of lipids in the mouse: plausible involvement of lingual CD36. : Obesity decreases the fat preference
2013
International audience; A relationship between orosensory detection of dietary lipids, regulation of fat intake, and body mass index was recently suggested. However, involved mechanisms are poorly understood. Moreover, whether obesity can directly modulate preference for fatty foods remains unknown. To address this question, exploration of the oral lipid sensing system was undertaken in diet-induced obese (DIO) mice. By using a combination of biochemical, physiological, and behavioral approaches, we found that i) the attraction for lipids is decreased in obese mice, ii) this behavioral change has an orosensory origin, iii) it is reversed in calorie-restricted DIO mice, revealing an inverse …
Cutting Edge: TGF-β Induces a Regulatory Phenotype in CD4+CD25− T Cells through Foxp3 Induction and Down-Regulation of Smad7
2004
Abstract CD4+CD25+ regulatory cells are a subpopulation of T lymphocytes of thymic origin. However, recent data suggest an alternative commitment of regulatory T cells in the periphery, although the precise mechanism is unknown. In the present work, we demonstrate that TGF-β is able to induce Foxp3 expression and subsequently a regulatory phenotype in CD4+CD25− peripheral murine T cells. Similarly, TGF-β induced Foxp3 in human CD4+CD25− T cells. Moreover, we show that the inhibitory Smad7 protein that is normally induced by TGF-β and limits TGF-β signaling, is strongly down-regulated by Foxp3 at the transcriptional level. Foxp3-mediated down-regulation of Smad7 subsequently rendered CD4+CD2…
Functionalized Polystyrene Nanoparticles Trigger Human Dendritic Cell Maturation Resulting in Enhanced CD4+T Cell Activation
2012
Nanoparticles (NP) represent a promising tool for biomedical applications. Here, sulfonate- and phosphonate-functionalized polystyrene NP are analyzed for their interaction with human monocyte-derived dendritic cells (DC). Immature dendritic cells (iDC) display a higher time- and dose-dependent uptake of functionalized polystyrene NP compared to mature dendritic cells (mDC). Notably, NP induce an enhanced maturation of iDC but not of mDC (upregulation of stimulatory molecules and cytokines). NP-triggered maturation results in a significantly enhanced T cell stimulatory capacity (increased CD4(+) T cell proliferation and IFN-γ production), indicating a shift to a pronounced Th1 response. Imm…
miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression.
2009
BackgroundIn humans and mice naturally occurring CD4(+)CD25(+) regulatory T cells (nTregs) are a thymus-derived subset of T cells, crucial for the maintenance of peripheral tolerance by controlling not only potentially autoreactive T cells but virtually all cells of the adaptive and innate immune system. Recent work using Dicer-deficient mice irrevocably demonstrated the importance of miRNAs for nTreg cell-mediated tolerance.Principal findingsDNA-Microarray analyses of human as well as murine conventional CD4(+) Th cells and nTregs revealed a strong up-regulation of mature miR-155 (microRNA-155) upon activation in both populations. Studying miR-155 expression in FoxP3-deficient scurfy mice …
Use of CD64 for the diagnosis of sepsis: a case-control study.
2010
CD64 is the high-affinity receptor of IgG. It is upregulated by inflammatory cytokines on neutrophils. The upregulation of CD64 is linked with PMN activation in SIRS or sepsis. Our aim is to verify these correlations.
Isolation of Differentially Expressed Genes in Epidermal Langerhans Cells
1997
Epidermal Langerhans cells (LC) represent immature dendritic cells (DC) resident in the skin, which are not yet able to prime naive T cells1. In vitro cultivation of LC in the presence of keratinocytes, supplying survival and differentiation signals, induces maturation events in LC2. These are highlighted by the downregulation of the biosynthesis of MHC class II molecules3, by the upregulation of the surface expression of adhesion and costimulatory molecules like CD80, CD86, CD54 and CD584,5, and by the acquisition of a potent immunostimulatory capacity for T cells6. Mature LC are potent inducers of naive T cells. Thus LC represent an ideal model system to investigate the maturation of DC (…
Abstract PO-46: Mechanisms of resistance to the PI3K inhibitor copanlisib in marginal zone lymphoma
2020
Abstract Background: PI3Kδ is expressed in B cells and has a central role in the B-cell receptor signaling. Copanlisib is a highly selective PI3Kδ and PI3Kα inhibitor, and it is currently under clinical development in indolent lymphomas including marginal zone lymphoma (MZL). Copanlisib is Food and Drug Administration (FDA) approved for the treatment of patients with relapsed or refractory follicular lymphoma. Nevertheless, a subset of patients can eventually relapse due to acquired resistance. A better understanding of resistance mechanisms could help to design improved therapies; hence, we generated MZL cell lines resistant to copanlisib. Materials and Methods: Cells were kept on copanlis…
TCDD deregulates contact inhibition in rat liver oval cells via Ah receptor, JunD and cyclin A.
2007
The aryl hydrocarbon receptor (AhR) is a transcription factor involved in physiological processes, but also mediates most, if not all, toxic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Activation of the AhR by TCDD leads to its dimerization with aryl hydrocarbon nuclear translocator (ARNT) and transcriptional activation of several phase I and II metabolizing enzymes. However, this classical signalling pathway so far failed to explain the pleiotropic hazardous effects of TCDD, such as developmental toxicity and tumour promotion. Thus, there is an urgent need to define genetic programmes orchestrated by AhR to unravel its role in physiology and toxicology. Here we show that TCDD …