Search results for "Cytometry"

Differentiative pathway activated by 3-aminobenzamide, an inhibitor of PARP, in human osteosarcoma MG-63 cells

2004

AbstractThis study describes the molecular mechanism by which treatment with 3-AB, a potent inhibitor of PARP, allows human osteosarcoma MG-63 cells to restrict growth and enter differentiation. Our findings show that in MG-63 cells, aberrant gene expression keeps Rb protein constitutively inactivated through hyperphosphorylation and this promotes uncontrolled proliferation of the cells. After 3-AB-treatment, the poly(ADP-ribosyl)ation of nuclear proteins markedly decreases and this results in an increase in both the hypophosphorylated active form of Rb and pRb/E2F complexes. These effects are accompanied by G1 arrest, downregulation of gene products required for proliferation (cyclin D1, β…

The transcriptional programme of contact-inhibition.

2010

Proliferation of non-transformed cells is regulated by cell-cell contacts, which are referred to as contact-inhibition. Vice versa, transformed cells are characterised by a loss of contact-inhibition. Despite its generally accepted importance for cell-cycle control, little is known about the intracellular signalling pathways involved in contact-inhibition. Unravelling the molecular mechanisms of contact-inhibition and its loss during tumourigenesis will be an important step towards the identification of novel target genes in tumour diagnosis and treatment. To better understand the underlying molecular mechanisms we identified the transcriptional programme of contact-inhibition in NIH3T3 fib…

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…

Synthetic Antitumor Vaccines from Tetanus Toxoid Conjugates of MUC1 Glycopeptides with the Thomsen-Friedenreich Antigen and a Fluorine-Substituted An…

2010

Carbocysteine counteracts the effects of cigarette smoke on cell growth and on the SIRT1/FoxO3 axis in bronchial epithelial cells

2016

Abstract Background Cigarette smoke may accelerate cellular senescence by increasing oxidative stress. Altered proliferation and altered expression of anti-aging factors, including SIRT1 and FoxO3, characterise cellular senescence. The effects of carbocysteine on the SIRT1/FoxO3 axis and on downstream molecular mechanisms in human bronchial epithelial cells exposed to cigarette smoke are largely unknown. Aims Aim of this study was to explore whether carbocysteine modulated SIRT1/FoxO3 axis, and downstream molecular mechanisms associated to cellular senescence, in a bronchial epithelial cell line (16-HBE) exposed to cigarette smoke. Methods 16HBE cells were stimulated with/without cigarette …

Cigarette smoke alters IL-33 expression and release in airway epithelial cells

2014

AbstractAirway epithelium is a regulator of innate immune responses to a variety of insults including cigarette smoke. Cigarette smoke alters the expression and the activation of Toll Like Receptor 4 (TLR4), an innate immunity receptor. IL-33, an alarmin, increases innate immunity Th2 responses. The aims of this study were to explore whether mini-bronchoalveolar lavage (mini-BAL) or sera from smokers have altered concentrations of IL-33 and whether cigarette smoke extracts (CSE) alter both intracellular expression (mRNA and protein) and release of IL-33 in bronchial epithelial cells. The role of TLR4 in the expression of IL-33 was also explored.Mini-BALs, but not sera, from smokers show red…

Multiple in vitro and in vivo regulatory effects of budesonide in CD4+ T lymphocyte subpopulations of allergic asthmatics.

2012

Abstract BACKGROUND: Increased activation and increased survival of T lymphocytes characterise bronchial asthma. OBJECTIVES: In this study the effect of budesonide on T cell survival, on inducible co-stimulator T cells (ICOS), on Foxp3 and on IL-10 molecules in T lymphocyte sub-populations was assessed. METHODS: Cell survival (by annexin V binding) and ICOS in total lymphocytes, in CD4+/CD25+ and in CD4+/CD25- and Foxp3 and IL-10 in CD4+/CD25+ and in CD4+/CD25-cells was evaluated, by cytofluorimetric analysis, in mild intermittent asthmatics (n = 19) and in controls (n = 15). Allergen induced T lymphocyte proliferation and the in vivo effects of budesonide in mild persistent asthmatics (n =…

The Cytokine GM-CSF Drives the Inflammatory Signature of CCR2+ Monocytes and Licenses Autoimmunity.

2015

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has emerged as a crucial cytokine produced by auto-reactive T helper (Th) cells that initiate tissue inflammation. Multiple cell types can sense GM-CSF, but the identity of the pathogenic GM-CSF-responsive cells is unclear. By using conditional gene targeting, we systematically deleted the GM-CSF receptor (Csf2rb) in specific subpopulations throughout the myeloid lineages. Experimental autoimmune encephalomyelitis (EAE) progressed normally when either classical dendritic cells (cDCs) or neutrophils lacked GM-CSF responsiveness. The development of tissue-invading monocyte-derived dendritic cells (moDCs) was also unperturbed upon Csf2r…

Defective expression of CD95 (FAS/APO-1) molecule suggests apoptosis impairment of T and B cells in HLA-B8, DR3-positive individuals.

1997

Activation-induced apoptosis is one of the primary control mechanisms for the negative selection of an immune response, leading to maintenance of immune homeostasis and selective T cell deletion. The interaction between the surface molecule Fas and its ligand (FasL) has been proposed as a primary mechanism initiating T cell apoptosis. The T cell receptor modulates the expression and function of these molecules. Defects in the Fas/FasL apoptosis pathway have been shown to result in autoimmune disease in humans and in murine models. Because subjects carrying the HLA-B8, DR3 haplotype show a number of immune dysfunctions, including membrano-proliferative glomerulonephritis, systemic lupus eryt…

Antigen-independent in vitro expansion of T cells does not affect the T cell receptor V beta repertoire.

1997

Analysis of the variable chains (V alpha/V beta) of the specific T cell receptor (TCR) of organ-infiltrating T cells may provide further insights into the pathogenesis of many infectious diseases, malignancies, and autoimmune disorders. To determine the TCR V beta repertoire of these small T cell populations antigen-independent in vitro expansion is necessary but may select for certain T cell subpopulations. In this study various antigen independent T cell activation protocols were used to stimulate peripheral blood mononuclear cells (PBMC) of six healthy blood donors, and TCR V beta molecules were analyzed by flow cytometry and semiquantitative reverse-transcriptase polymerase chain reacti…