Search results for "ACTIVATION"
showing 10 items of 2079 documents
HSP60 and CpG-DNA-oligonucleotides differentially regulate LPS-tolerance of hepatic Kupffer cells
2004
Background/aims: Hepatic Kupffer cells (KC) are major regulators of the immune response to gut-derived bacterial products; uncontrolled activation of KC by bacterial components is of pathogenic relevance in alcoholic hepatitis and septic shock. Methods: We examined the role of bacterial lipopolysaccharide (LPS), bacterial and autologous HSP60 and bacterial DNA, which are recognized by innate Toll-like receptors, during activation of murine KC. Results: In cultivated KC, autologous HSP60 induced a state of LPS-hyporesponsiveness; bacterial DNA did not mitigate the response to subsequent LPS-challenge in vitro; in contrast, pre-treatment of mice with bacterial DNA even significantly increased…
A role for Toll-like receptor mediated signals in neutrophils in the pathogenesis of the anti-phospholipid syndrome.
2012
The anti-phospholipid syndrome (APS) is characterized by recurrent thrombosis and occurrence of anti-phospholipid antibodies (aPL). aPL are necessary, but not sufficient for the clinical manifestations of APS. Growing evidence suggests a role of innate immune cells, in particular polymorphonuclear neutrophils (PMN) and Toll-like receptors (TLR) to be additionally involved. aPL activate endothelial cells and monocytes through a TLR4-dependent signalling pathway. Whether this is also relevant for PMN in a similar way is currently not known. To address this issue, we used purified PMN from healthy donors and stimulated them in the presence or absence of human monoclonal aPL and the TLR4 agonis…
LTB4 is present in exudative pleural effusions and contributes actively to neutrophil recruitment in the inflamed pleural space
2004
SUMMARY The pleural space is a virtual compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells during a variety of respiratory diseases. Here, we study the potential role of the eicosanoid metabolite leukotriene B4 (LTB4) in disparate diseases leading to acute (pneumonia) or chronic (tuberculosis, cancer) inflammation of the pleural space. LTB4 concentrations were significantly higher in pleural fluid due to pneumonia, tuberculosis and cancer with respect to congestive heart failure and correlated with neutrophil elastase, which is used as an indication of state of activation of neutrophils in the pleural space. Moreover, pleural LTB4 was biological…
Rho protein inhibition blocks protein kinase C translocation and activation.
1998
Small GTP-binding proteins of the Ras and Rho family participate in various important signalling pathways. Large clostridial cytotoxins inactivate GTPases by UDP-glucosylation. Using Clostridium difficile toxin B-10463 (TcdB) for inactivation of Rho proteins (RhoA/Rac/Cdc42) and Clostridium sordellii lethal toxin-1522 (TcsL) for inactivation of Ras-proteins (Ras/Rac/Ral, Rap) the role of these GTPases in protein kinase C (PKC) stimulation was studied. Phorbol-myristate-acetate (PMA) induced a rapid PKC translocation to and activation in the particulate cell fraction as determined by PKC-activity measurements and Western blots for PKC alpha. These effects were blocked by TcdB inhibiting Rho …
Release of IL-12 by dendritic cells activated by TLR ligation is dependent on MyD88 signaling, whereas TRIF signaling is indispensable for TLR synerg…
2010
Abstract Synergistic activation of dendritic cells by combinations of TLR ligands requires both MyD88- and TRIF-dependent signaling. Recently, it has been shown that certain combinations of TLR ligands act in synergy to induce the release of IL-12 by DCs. In this study, we sought to define the critical parameters underlying TLR synergy. Our data show that TLR ligands act synergistically if MyD88- and TRIF-dependent ligands are combined. TLR4 uses both of these adaptor molecules, thus activation via TLR4 proved to be a synergistic event on its own. TLR synergy did not affect all aspects of DC activation but enhanced primarily the release of certain cytokines, particularly IL-12, whereas the …
Terpioside B, a difucosyl GSL from the marine sponge Terpios sp. is a potent inhibitor of NO release.
2010
Terpioside B (2a), a unique glycolipid containing two fucose residues in the furanose form in its pentasaccharide chain, was isolated from the marine sponge Terpios sp. Its complete stereostructure was solved by interpretation of mass spectrometric and NMR data along with CD and GG-MS analyses of its degradation products. Terpioside B is a potent inhibitor against LPS-induced NO release, and is considerably more active than simpler glycosphingolipids such as terpioside A and monoglucosylceramide.
Prostaglandin E2 regulates inducible nitric oxide synthase in the murine macrophage cell line J774.
1995
We have evaluated the role of prostaglandin E2 (PGE2) in the synthesis of nitric oxide (NO) by the activation of the inducible form of nitric oxide synthase (NOS) in the murine macrophage cell line, J774, stimulated with different doses of lipopolysaccharide (LPS). The stimulation of the J774 line with suboptimal doses of LPS (0.1 microgram/mL) caused a production of endogenous PGE2 that was capable of stimulating NOS activity inducing an increase in the NO synthesis, as attested by the fact that cyclooxygenase enzyme inhibitor, indomethacin, significantly reduced NO secretion. On the contrary, a higher dose of LPS (1 microgram/mL) produced high levels of PGE2 that reduced the levels of NOS…
Modeling the isothermal inactivation curves of Listeria innocua CECT 910 in a vegetable beverage under low-temperature treatments and different pH le…
2015
Thermal inactivation kinetics of Listeria innocua CECT 910 inoculated in a vegetable beverage at three pH conditions (4.25, 4.75, and 5.20), four levels of temperature (50, 55, 60, 65℃), and different treatment times (0–75 min) were obtained. Survival curves did not follow a log-linear relationship and consequently were fitted to various mathematical models: Weibull, Geeraerd, Cerf with shoulder, and the modified Gompertz equation. Results indicated that the best model for the treatment conditions was the modified Gompertz equation, which provides the best goodness-of-fit and the lowest Akaike information criterion value. Sensitivity analysis indicated that the most influential factors affe…
Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices
2019
Fibrosis is the hallmark of pathologic tissue remodelling in most chronic diseases. Despite advances in our understanding of the mechanisms of fibrosis, it remains uncured. Fibrogenic processes share conserved core cellular and molecular pathways across organs. In this study, we aimed to elucidate shared and organ-specific features of fibrosis using murine precision-cut tissue slices (PCTS) prepared from small intestine, liver and kidneys. PCTS displayed substantial differences in their baseline gene expression profiles: 70% of the extracellular matrix (ECM)-related genes were differentially expressed across the organs. Culture for 48 h induced significant changes in ECM regulation and trig…
Interleukin-33-Dependent Innate Lymphoid Cells Mediate Hepatic Fibrosis
2013
SummaryLiver fibrosis is a consequence of chronic liver diseases and thus a major cause of mortality and morbidity. Clinical evidence and animal studies suggest that local tissue homeostasis is disturbed due to immunological responses to chronic hepatocellular stress. Poorly defined stress-associated inflammatory networks are thought to mediate gradual accumulation of extracellular-matrix components, ultimately leading to fibrosis and liver failure. Here we have reported that hepatic expression of interleukin-33 (IL-33) was both required and sufficient for severe hepatic fibrosis in vivo. We have demonstrated that IL-33’s profibrotic effects related to activation and expansion of liver resi…