Search results for "g factor"
showing 10 items of 514 documents
Granulocyte Colony-Stimulating Factor Nanocarriers for Stimulation of the Immune System (Part I): Synthesis and Biodistribution Studies
2018
In the field of cancer immunotherapy, an original approach consists of using granulocyte colony-stimulating factor (G-CSF) to target and activate neutrophils, cells of the innate immune system. G-CSF is a leukocyte stimulating molecule which is commonly used in cancer patients to prevent or reduce neutropenia. We focused herein on developing a G-CSF nanocarrier which could increase the in vivo circulation time of this cytokine, keeping it active for targeting the spleen, an important reservoir of neutrophils. G-CSF-functionalized silica and gold nanoparticles were developed. Silica nanoparticles of 50 nm diameter were functionalized by a solid phase synthesis approach. The technology enable…
Vitamin C blocks inflammatory platelet-activating factor mimetics created by cigarette smoking.
1997
Cigarette smoking within minutes induces leukocyte adhesion to the vascular wall and formation of intravascular leukocyte-platelet aggregates. We find this is inhibited by platelet-activating factor (PAF) receptor antagonists, and correlates with the accumulation of PAF-like mediators in the blood of cigarette smoke-exposed hamsters. These mediators were PAF-like lipids, formed by nonenzymatic oxidative modification of existing phospholipids, that were distinct from biosynthetic PAF. These PAF-like lipids induced isolated human monocytes and platelets to aggregate, which greatly increased their secretion of IL-8 and macrophage inflammatory protein-1alpha. Both events were blocked by a PAF r…
A Neuroprotective Function for the Hematopoietic Protein Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
2007
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine responsible for the proliferation, differentiation, and maturation of cells of the myeloid lineage, which was cloned more than 20 years ago. Here we uncovered a novel function of GM-CSF in the central nervous system (CNS). We identified the GM-CSF α-receptor as an upregulated gene in a screen for ischemia-induced genes in the cortex. This receptor is broadly expressed on neurons throughout the brain together with its ligand and induced by ischemic insults. In primary cortical neurons and human neuroblastoma cells, GM-CSF counteracts programmed cell death and induces BCL-2 and BCL-Xl expression in a dose- a…
CTCF and BORIS Regulate Rb2/p130 Gene Transcription: A Novel Mechanism and a New Paradigm for Understanding the Biology of Lung Cancer
2011
Abstract Although innumerable investigations regarding the biology of lung cancer have been carried out, many aspects thereof remain to be addressed, including the role played by the retinoblastoma-related protein Rb2/p130 during the evolution of this disease. Here we report novel findings on the mechanisms that control Rb2/p130 gene expression in lung fibroblasts and characterize the effects of Rb2/p130 deregulation on the proliferative features of lung cancer cells. We revealed for the first time that in lung fibroblasts the expression of Rb2/p130 gene is directly controlled by the chromatin insulator CCCTC-binding factor, CTCF, which by binding to the Rb2/p130 gene promoter induces, and/…
7C: Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs.
2019
Abstract Background Knowledge of the three-dimensional structure of the genome is necessary to understand how gene expression is regulated. Recent experimental techniques such as Hi-C or ChIA-PET measure long-range chromatin interactions genome-wide but are experimentally elaborate, have limited resolution and such data is only available for a limited number of cell types and tissues. Results While ChIP-seq was not designed to detect chromatin interactions, the formaldehyde treatment in the ChIP-seq protocol cross-links proteins with each other and with DNA. Consequently, also regions that are not directly bound by the targeted TF but interact with the binding site via chromatin looping are…
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…
Tumorigenic conversion of endothelial cells.
2003
Tumors of endothelial origin develop rarely. Until now, only two angiosarcoma (AS)-derived endothelial cell lines have been be isolated, ISO-HAS and AS-M. Both AS-derived endothelial cell lines presented the typical endothelial characteristics, such as the expression of CD31 and von Willebrand factor, but differed from normal endothelial cells in a nuclear expression of p53, in a delayed angiogenic reaction, and a reduced expression of caveolin. In addition, differences in the expression of cytokines and cell adhesion molecules responsive to proinflammatory stimuli were observed. While AS-M showed an expression pattern similar to that of human umbilical vein endothelial cells (HUVEC), ISO-H…
Impact of Glutathione Peroxidase-1 Deficiency on Macrophage Foam Cell Formation and Proliferation: Implications for Atherogenesis
2013
Clinical and experimental evidence suggests a protective role for the antioxidant enzyme glutathione peroxidase-1 (GPx-1) in the atherogenic process. GPx-1 deficiency accelerates atherosclerosis and increases lesion cellularity in ApoE(-/-) mice. However, the distribution of GPx-1 within the atherosclerotic lesion as well as the mechanisms leading to increased macrophage numbers in lesions is still unknown. Accordingly, the aims of the present study were (1) to analyze which cells express GPx-1 within atherosclerotic lesions and (2) to determine whether a lack of GPx-1 affects macrophage foam cell formation and cellular proliferation. Both in situ-hybridization and immunohistochemistry of l…
The gp130-stimulating designer cytokine hyper-IL-6 promotes the expansion of human hematopoietic progenitor cells capable to differentiate into funct…
2000
Abstract Objective . Hyper-IL-6, a fusion protein of interleukin-6 and its specific receptor, together with stem cell factor leads to the proliferation of primitive hematopoietic progenitor cells. Based on these findings, the current study examined whether hyper-IL-6 promotes the growth of precursor cells that can be further differentiated into dendritic cells in the presence of additional cytokines. Methods . Dendritic cell cultures were generated from CD34 + hematopoietic progenitor cells derived either from bone marrow or from peripheral blood. CD34 + cells were cultured in the presence of cytokines for 2 weeks and then used for phenotyping and T-cell stimulation assays. Results . Hyper-…
Hematopoietic Growth Factors Are Differentially Regulated in Monocytes and CD4+T Lymphocytes: Influence of IFN-α and Interleukin-4
1998
We investigated the influence of interferon-alpha (IFN-alpha) on the synthesis of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) by monocytes and activated T helper cells. IFN-alpha inhibited the production of GM-CSF in unstimulated and lipopolysaccharide (LPS)-activated monocytes to the same extent as was observed in the presence of IL-4. In highly purified CD4+ T cells, which were activated by incubation with immobilized anti-CD3 antibody and anti-CD28, IFN-alpha reduced production of GM-CSF to 47%. In contrast, GM-CSF production in activated T cells was unaffected by exogenously added IL-4. The production of IL-3 by T helper cells was significantly inh…