Search results for "tumor necrosis factor-alpha"
showing 10 items of 504 documents
Barrier functions and paracellular integrity in human cell culture models of the proximal respiratory unit.
2009
International audience; Airway epithelial cells provide a barrier to the translocation of inhaled materials. Tight (TJ) and adherens junctions (AJ) play a key role in maintaining barrier functions, and are responsible for the selective transport of various substances through the paracellular pathway. In this study we compared a bronchial cell line (16HBE14o-) and primary bronchial cells (HBEC), both cocultivated with the fibroblast cell line Wi-38, with respect to their structural differentiation and their reaction to cytokine stimulation. HBEC formed a pseudostratified epithelial layer and expressed TJ and AJ proteins after 2 weeks in coculture. Mucus-producing and ciliated cells were foun…
Mast cell-derived mediators promote murine neutrophil effector functions
2013
Mast cells are able to trigger life-saving immune responses in murine models for acute inflammation. In such settings, several lines of evidence indicate that the rapid and protective recruitment of neutrophils initiated by the release of mast cell-derived pro-inflammatory mediators is a key element of innate immunity. Herein, we investigate the impact of mast cells on critical parameters of neutrophil effector function. In the presence of activated murine bone marrow-derived mast cells, neutrophils freshly isolated from bone marrow rapidly lose expression of CD62L and up-regulate CD11b, the latter being partly driven by mast cell-derived TNF and GM-CSF. Mast cells also strongly enhance neu…
Reduction of tumor necrosis factor-alpha (TNF-α) related nuclear factor-kappaB (NF-κB) translocation but not inhibitor kappa-B (Iκ-B)-degradation by …
2002
Degradation of inhibitor kappa-B (Ikappa-B) followed by translocation of nuclear factor-kappaB (NF-kappaB) into the nucleus and activation of gene expression is essential in tumor necrosis factor-alpha (TNF-alpha)-signaling. In order to analyze the role of Rho proteins in TNF-alpha-induced NF-kappaB-activation in human umbilical cord vein endothelial cells (HUVEC) we used Clostridium difficile toxin B-10463 (TcdB-10463) which inactivates RhoA/Rac1/Cdc42 by glucosylation and Clostridium botulinum C3-toxin which inhibits RhoA/B/C by ADP-ribosylation. Exposure of HUVEC to 10 ng/mL TcdB-10463 or 2.5 microg/mL C3-toxin inhibited TNF-alpha (100 ng/mL)-induced expression of a NF-kappaB-dependent r…
Pentoxifylline in liver ischemia and reperfusion.
2013
Pentoxifylline is a methylxanthine compound which was first filed in 1973 and registered in 1974 in the United States by Sanofi-Aventis Deustchland Gmbh for the treatment of intermittent claudication for chronic occlusive arterial disease. This methylxanthine was later discovered to be a phosphodiesterase inhibitor. Furthermore, its hemorheological properties and its function as an inhibitor of inflammatory cytokines, like TNF- α, allowed researchers to study its effects in organ ischemia and reperfusion and transplantation. Although this drug has demonstrated beneficial effects, the mechanisms by which Pentoxifylline exerts a protective effect are not fully understood. This paper focuses o…
Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-gamma and TNF-alpha production.
2001
Interleukin (IL)-18, initially described as interferon (IFN)-gamma-inducing factor, is expressed in the inflamed mucosa of patients with Crohn's disease. To investigate the role of IL-18 in intestinal inflammation, the effect of neutralizing antimurine IL-18 antiserum in dextran sulfate sodium (DSS)-induced colitis in BALB/c and C57BL/6 mice was examined. During a dose response of DSS, levels of colonic IL-18 increased parallel with clinical worsening. With the use of confocal laser microscopy, the increased IL-18 was localized to the intestinal epithelial layer. Anti-IL-18 treatment resulted in a dose-dependent reduction of the severity of colitis in both BALB/c and C57BL/6 mice. Colon sho…
Enhanced in vivo targeting of murine nonparenchymal liver cells with monophosphoryl lipid A functionalized microcapsules.
2014
A broad spectrum of infectious liver diseases emphasizes the need of microparticles for targeted delivery of immunomodulatory substances to the liver. Microcapsules (MCs) are particularly attractive for innovative drug and vaccine formulations, enabling the combination of antigen, drugs, and adjuvants. The present study aimed to develop microcapsules characterized by an enhanced liver deposition and accelerated uptake by nonparenchymal liver cells (NPCs). Initially, two formulations of biodegradable microcapsules were synthesized from either hydroxyethyl starch (HES) or mannose. Notably, HES-MCs accumulated primarily in the liver, while mannose particles displayed a lung preference. Functio…
Regulation of tumour cell sensitivity to TNF-induced oxidative stress and cytotoxicity: Role of glutathione
1998
Glutathione (GSH) and the rate of cellular proliferation determine tumour cell sensitivity to tumour necrosis factor (TNF). Buthionine sulphoximine (BSO), a selective inhibitor of GSH synthesis, inhibits tumour growth and increases recombinant human TNF (rhTNF)-alpha cytoxicity in vitro. Administration of sublethal doses of rhTNF-alpha to Ehrlich ascites-tumour (EAT)-bearing mice induces oxidative stress (as measured by increases in intracellular peroxide levels, O2.- generation and mitochondrial GSSG). ATP-induced selective GSH depletion, when combined with rhTNF-alpha administration, affords a 61% inhibition of tumour growth and results in a significant extent of host survival. Administra…
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…