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Strong Inducer (strong + inducer)

Distribution by Scientific Domains

Medical Sciences	40%
Chemistry	40%

Selected Abstracts

Effect of drug-induced cytotoxicity on glucose uptake in Hodgkin's lymphoma cells

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2006
Ursula Banning
Abstract:,Background:,In Hodgkin's lymphoma, F-18-fluoro-deoxy- d -glucose positron emission tomography (FDG-PET) is used for staging and response evaluation after chemotherapy. However, drug-mediated downregulation of glucose uptake in viable Hodgkin's lymphoma cells might limit the use of FDG-PET. Methods:,We analyzed the effect of etoposide on cell viability and uptake of F-18-fluoro-deoxy- d -glucose or the glucose analog 2-[N -(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) in vitro. Results:,Etoposide induced a dose-dependent cytotoxicity in HDLM-2 cells which was significantly correlated with reduced FDG uptake. However, it also significantly increased the portion of viable cells which did not take up 2-NBDG. Interestingly, etoposide-induced cytotoxicity was mainly mediated via caspase-dependent mechanisms, whereas the cell death induced by deprivation of glucose was mediated via caspase-independent mechanisms. Conclusion:,Etoposide-mediated reduction of glucose uptake by Hodgkin's lymphoma cells is mainly caused by cell death. In a small fraction of viable cells, etoposide might downregulate glucose transporters and/or hexokinase activity and by that inhibit glucose uptake. This, however, might not lead to false-negative results of response evaluation in Hodgkin's lymphoma patients after chemotherapy, because inhibition of glucose uptake itself seems to be a strong inducer of cell death. Altogether, this study provides important in vitro evidence to clarify the mechanisms by which FDG-PET monitors the effect of anti-cancer treatment in Hodgkin's lymphoma patients. [source]

Transcriptional upregulation of inflammatory cytokines in human intestinal epithelial cells following Vibrio cholerae infection

FEBS JOURNAL, Issue 17 2007
Arunava Bandyopadhaya
Coordinated expression and upregulation of interleukin-1,, interleukin-1,, tumor necrosis factor-,, interleukin-6, granulocyte,macrophage colony-stimulating factor, interleukin-8, monocyte chemotactic protein-1 (MCP-1) and epithelial cell derived neutrophil activator-78, with chemoattractant and proinflammatory properties of various cytokine families, were obtained in the intestinal epithelial cell line Int407 upon Vibrio cholerae infection. These proinflammatory cytokines also showed increased expression in T84 cells, except for interleukin-6, whereas a striking dissimilarity in cytokine expression was observed in Caco-2 cells. Gene expression studies of MCP-1, granulocyte,macrophage colony-stimulating factor, interleukin-1,, interleukin-6 and the anti-inflammatory cytokine transforming growth factor-, in Int407 cells with V. cholerae culture supernatant, cholera toxin, lipopolysaccharide and ctxA mutant demonstrated that, apart from cholera toxin and lipopolysaccharide, V. cholerae culture supernatant harbors strong inducer(s) of interleukin-6 and MCP-1 and moderate inducer(s) of interleukin-1, and granulocyte,macrophage colony-stimulating factor. Cholera toxin- or lipopolysaccharide-induced cytokine expression is facilitated by activation of nuclear factor-,B (p65 and p50) and cAMP response element-binding protein in Int407 cells. Studies with ctxA mutants of V. cholerae revealed that the mutant activates the p65 subunit of nuclear factor-,B and cAMP response element-binding protein, and as such the activation is mediated by cholera toxin-independent factors as well. We conclude that V. cholerae elicits a proinflammatory response in Int407 cells that is mediated by activation of nuclear factor-,B and cAMP response element-binding protein by cholera toxin, lipopolysaccharide and/or other secreted products of V. cholerae. [source]

Microglial expression of ,v,3 and ,v,5 integrins is regulated by cytokines and the extracellular matrix: ,5 Integrin null microglia show no defects in adhesion or MMP-9 expression on vitronectin

GLIA, Issue 7 2009
Richard Milner
Abstract As the primary immune effector cells in the CNS, microglia play a central role in regulating inflammation. The extracellular matrix (ECM) protein vitronectin is a strong inducer of microglial activation, switching microglia from a resting into an activated potentially destructive phenotype. As the activating effect of vitronectin is mediated by ,v integrins, the aim of the current study was to evaluate the requirement of the ,v,5 integrin in mediating microglial adhesion and activation to vitronectin, by studying these events in ,5 integrin-null murine microglia. Surprisingly, ,5 integrin null microglia were not defective in adhesion to vitronectin. Further analysis showed that microglia express the ,v,3 integrin, in addition to ,v,5. Flow cytometry revealed that microglial ,v integrin expression is regulated by cytokines and ECM proteins. ,v,3 integrin expression was downregulated by IFN-,, TNF, LPS, and TGF-,1. ,v,5 expression was also reduced by IFN-,, TNF, and LPS, but strongly increased by the antiactivating factors TGF-,1 and laminin. Gel zymography revealed that ,5 integrin null microglia showed no deficiency in their expression of matrix metalloproteinase (MMP)-9 in response to vitronectin. Taken together, these data show that microglia express two different ,v integrins, ,v,3 and ,v,5, and that expression of these integrins is independently regulated by cytokines and ECM proteins. Furthermore, it reveals that the ,v,5 integrin is not essential for mediating microglial adhesion and MMP-9 expression in response to vitronectin. © 2008 Wiley-Liss, Inc. [source]

The myeloid-related proteins 8 and 14 complex, a novel ligand of toll-like receptor 4, and interleukin-1, form a positive feedback mechanism in systemic-onset juvenile idiopathic arthritis

ARTHRITIS & RHEUMATISM, Issue 3 2009
Michael Frosch
Objective Fever of unknown origin is a diagnostic challenge in children, especially for differentiation of systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) and infectious diseases. We undertook this study to analyze the relevance of myeloid-related proteins (MRPs) 8 and 14, endogenous activators of Toll-like receptor 4, in diagnosis and pathogenesis of systemic-onset JIA. Methods Serum concentrations of MRP-8/MRP-14 were analyzed in 60 patients with systemic-onset JIA, 85 patients with systemic infections, 40 patients with acute lymphoblastic leukemia, 5 patients with acute myeloblastic leukemia, 18 patients with neonatal-onset multisystem inflammatory disease (NOMID), and 50 healthy controls. In addition, we investigated the link between interleukin-1, (IL-1,) and MRP-8/MRP-14 in systemic-onset JIA. Results Serum MRP-8/MRP-14 concentrations were significantly (P < 0.001) elevated in patients with active systemic-onset JIA (mean ± 95% confidence interval 14,920 ± 4,030 ng/ml) compared with those in healthy controls (340 ± 70 ng/ml), patients with systemic infections (2,640 ± 720 ng/ml), patients with acute lymphoblastic leukemia (650 ± 280 ng/ml), patients with acute myeloblastic leukemia (840 ± 940 ng/ml), and patients with NOMID (2,830 ± 580 ng/ml). In contrast to C-reactive protein levels, MRP-8/MRP-14 concentrations distinguished systemic-onset JIA from infections, with a specificity of 95%. MRP-14 in serum of patients with systemic-onset JIA was a strong inducer of IL-1, expression in phagocytes. Conclusion The analysis of MRP-8/MRP-14 in serum is an excellent tool for the diagnosis of systemic-onset JIA, allowing early differentiation between patients with systemic-onset JIA and those with other inflammatory diseases. MRP-8/MRP-14 and IL-1, represent a novel positive feedback mechanism activating phagocytes via 2 major signaling pathways of innate immunity during the pathogenesis of systemic-onset JIA. [source]

Crystal structure of achiral nonapeptide Boc,(Aib,,zPhe)4,Aib,OMe at atomic resolution: Evidence for a 310 -helix

BIOPOLYMERS, Issue 3 2003
Yoshihito Inai
Abstract An x-ray crystallographic analysis was carried out for Boc,(Aib,,ZPhe)4,Aib,OMe (1: Boc = t -butoxycarbonyl; Aib = ,-aminoisobutyric acid; ,ZPhe = Z -,,,-didehydrophenylalanine) to provide the precise conformational parameters of the octapeptide segment ,(Aib,,ZPhe)4,. Peptide 1 adopted a typical 310 -helical conformation characterized by ,,, = ±55.8° (50°,65°), ,,, = ±26.7° (15°,45°), and ,,, = ±179.5° (168°,188°) for the average values of the ,(Aib,,ZPhe)4, segment (the range of the eight values). The 310 -helix contains 3.1 residues per turn, being close to the "perfect 310 -helix" characterized by 3.0 residues per turn. NMR and Fourier transform infrared (FTIR) spectroscopy revealed that the 310 -helical conformation at the atomic resolution is essentially maintained in solution. Energy minimization of peptide 1 by semiempirical molecular orbital calculation converged to a 310 -helical conformation similar to the x-ray crystallographic 310 -helix. The preference for a 310 -helix in the ,(Aib,,ZPhe)4, segment is ascribed to strong inducers of the 310 -helix inherent in Aib and ,ZPhe residues,in particular, the Aib residues tend to stabilize a 310 -helix more effectively. Therefore, the ,(Aib,,ZPhe)4, segment is useful to rationally design an optically inactive 310 -helical backbone, which will be of great importance to provide novel insights into noncovalent and covalent chiral interactions of a helical peptide with a chiral molecule. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 310,322, 2003 [source]