Search results for "tumor necrosis factor alpha"
showing 10 items of 479 documents
Cell death and hepatocarcinogenesis: Dysregulation of apoptosis signaling pathways
2011
Hepatocellular carcinoma (HCC) remains a disease with a poor prognosis despite recent advances in the pathophysiology and treatment. Although the disease is biologically heterogeneous, dysregulation of cellular proliferation and apoptosis both occur frequently and contribute to the malignant phenotype. Chronic liver disease is associated with intrahepatic inflammation which promotes dysregulation of cellular signaling pathways; this triggers proliferation and thus lays the ground for expansion of premalignant cells. Cancer emerges when immunological control fails and transformed cells develop resistance against cell death signaling pathways. The same mechanisms underlie the poor responsiven…
Lysosomal degradation of the carboxydextran shell of coated superparamagnetic iron oxide nanoparticles and the fate of professional phagocytes
2010
Contrast agents based on dextran-coated superparamagnetic iron oxide nanoparticles (SPIO) are internalized by professional phagocytes such as hepatic Kupffer cells, yet their role in phagocyte biology remains largely unknown. Here we investigated the effects of the SPIO ferucarbotran on murine Kupffer cells and human macrophages. Intravenous injection of ferucarbotran into mice led to rapid accumulation of the particles in phagocytes and to long-lasting increased iron deposition in liver and kidneys. Macrophages incorporate ferucarbotran in lysosomal vesicles containing α-glucosidase, which is capable of degrading the carboxydextran shell of the ferucarbotran particles. Intravenous injectio…
Apoptosis of T cells and the control of inflammatory bowel disease: therapeutic implications.
2007
Inflammatory bowel diseases (IBDs) such as Crohn’s disease and ulcerative colitis are the result of an imbalanced mucosal T cell response. Despite the identification of a genetic susceptibility region in the NOD2/CARD15 (nucleotide-binding oligomerisation domain 2/caspase recruitment domain 15) gene, the aetiology is still unclear. Thus, the hunt for disease-initiating factors such as defects in the mucosal barrier or pathogenic microorganisms is ongoing. By contrast, the immunopathogenesis in IBDs is better understood. The identification of cytokines that are involved in T cell and monocyte signalling led to specific therapeutic concepts. Recent data have clearly shown that the most powerf…
Caspase-8 regulates TNF-alpha induced epithelial necroptosis and terminal ileitis
2011
Two groups identify the regulation of death-receptor-induced necroptosis as an epithelial intrinsic mechanism that is important for the maintenance of immune homeostasis and the prevention of intestinal inflammation in mice. Welz et al. describe an unexpected physiological function for FADD (Fas-associated protein with death domain), an adaptor protein required for death-receptor-induced apoptosis. Mice with intestinal epithelial specific knockout of FADD develop severe colon inflammation due to increased death of FADD-deficient colonic epithelial cells. Gunther et al. report a novel and unexpected function of caspase-8 in maintaining immune homeostasis in the gut. Caspase-8 expression by g…
Selective targeting of activated T cells in chronic intestinal inflammation
2009
Programmed cell death (apoptosis) has been implicated in normal biological processes as well as in the pathology of human diseases.1 The characterisation of genes involved in apoptosis has been pursued intensively and led to the identification of two major classes of genes: the bcl-2 family and the caspase family. Caspases are proteases that cleave their target substrates at specific peptide sequences and during apoptosis the activation of caspases takes place in a cascade fashion, leading to nuclear engulfment and cell death. Thus, caspases represent key functional components of the apoptosis pathway in human cells. Resistance against apoptosis is a key phenomenon in various chronic inflam…
Interferons increase cell resistance to Staphylococcal alpha-toxin.
2007
ABSTRACTMany bacterial pathogens, includingStaphylococcus aureus, use a variety of pore-forming toxins as important virulence factors. Staphylococcal alpha-toxin, a prototype β-barrel pore-forming toxin, triggers the release of proinflammatory mediators and induces primarily necrotic death in susceptible cells. However, whether host factors released in response to staphylococcal infections may increase cell resistance to alpha-toxin is not known. Here we show that prior exposure to interferons (IFNs) prevents alpha-toxin-induced membrane permeabilization, the depletion of ATP, and cell death. Moreover, pretreatment with IFN-α decreases alpha-toxin-induced secretion of interleukin 1β (IL-1β)…
Role Of S-Nitrosylation In The Extrinsic Apoptotic Signalling Pathway In Cancer.
2015
One of the key features of tumour cells is the acquisition of resistance to apoptosis. Thus, determining therapeutic strategies that circumvent apoptotic resistance and result in tumor regression is a challenge. One strategy to induce apoptosis is to activate death receptor signalling pathways. Members of the Tumor Necrosis Factor TNF-family death receptors ligand (TRAIL, FasL and TNF-α) can originate from immune and non-immune cells. Death receptors, engaged by cognate ligands, can initiate multiple signaling pathways, which can generate diverse outcomes, including non-apoptosis-related signal. Knowledge on the molecular mechanisms (that determine death or survival of tumour cells) followi…
Effect of cilomilast (Ariflo) on TNF-α, IL-8, and GM-CSF release by airway cells of patients with COPD
2003
Background: Inflammation in chronic obstructive pulmonary disease (COPD) is characterised by increased neutrophilic infiltration of the airways. Cilomilast, a novel selective phosphodiesterase 4 inhibitor in clinical development for COPD treatment, exerts anti-inflammatory effects. The ability of cilomilast to inhibit the release of neutrophil chemoattractants such as tumour necrosis factor (TNF)-α, interleukin (IL)-8, and granulocyte-macrophage colony stimulating factor (GM-CSF) by bronchial epithelial cells and sputum cells isolated from 10 patients with COPD, 14 normal controls, and 10 smokers was investigated. Methods: Bronchial epithelial cells obtained by bronchial brushing and sputum…
Mast cell-derived tumour necrosis factor is essential for allergic airway disease
2007
Mast cells are thought to contribute to allergic airway disease. However, the role of mast cell-produced mediators, such as tumour necrosis factor (TNF), for the development of allergic airway disease is unclear. In order to define the role of mast cells in acute allergic airway disease two strains of mast cell-deficient mice (Kit W/Wv and Kit W-sh/W-sh ) were studied. Compared with their wild-type littermates, Kit W/Wv and Kit W-sh/W-sh mice developed significantly lower airway responsiveness to methacholine and less airway inflammation and goblet cell metaplasia, following sensitisation in the absence of adjuvant and airway challenge. Transfer of bone marrow-derived mast cells (BMMCs) fro…
Antitumour activity of mononuclear phagocytes: role of tumour necrosis factor alpha.
1992
Tumour necrosis factor alpha (TNF) is a cytokine produced by mononuclear phagocytes (MP) originally discovered for its cytotoxic activity on tumour cell targets. It was subsequently demonstrated that, in addition to its oncolytic potential, TNF exerts a wide variety of activities on the host defensive system against malignancies. This article briefly reviews the current concepts on the role of TNF in the antitumour activity of MP.