A5067599146- Advanced Glycation End Products research
- Blood Coagulation and Thrombosis Mechanisms
- Pain Mechanisms and Treatments
- Chronic Kidney Disease and Diabetes
- Diet and metabolism studies
- Adipokines, Inflammation, and Metabolic Diseases
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Biochemical effects in animals
- Botulinum Toxin and Related Neurological Disorders
- Venous Thromboembolism Diagnosis and Management
- Natural Antidiabetic Agents Studies
- Cell Adhesion Molecules Research
- Diabetes and associated disorders
- S100 Proteins and Annexins
- Immune Response and Inflammation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Diabetes Treatment and Management
- Neurological Disorders and Treatments
- Protease and Inhibitor Mechanisms
- Angiogenesis and VEGF in Cancer
- Liver Disease Diagnosis and Treatment
- Pancreatic function and diabetes
- Alcohol Consumption and Health Effects
Heidelberg University
2016-2025
University Hospital Heidelberg
2016-2025
German Center for Diabetes Research
2015-2024
Heinrich Heine University Düsseldorf
2014-2024
Deutsches Diabetes-Zentrum e.V.
2014-2024
TU Dresden
1997-2024
German Center for Lung Research
2024
Diabetesinstitut Heidelberg
2018-2023
Technical University of Munich
2004-2022
Helmholtz Zentrum München
2016-2022
S100/calgranulin polypeptides are present at sites of inflammation, likely released by inflammatory cells targeted to such loci a range environmental cues. We report here that receptor for AGE (RAGE) is central cell surface EN-RAGE (extracellular newly identified RAGE-binding protein) and related members the superfamily. Interaction EN-RAGEs with cellular RAGE on endothelium, mononuclear phagocytes, lymphocytes triggers activation, generation key proinflammatory mediators. Blockade...
Tumor necrosis factor/cachectin (TNF) is a mediator of the septic state, which involves diffuse abnormalities coagulation throughout vasculature. Since previous studies have shown that endothelial cells can play an active role in coagulation, we wished to determine whether TNF could modulate cell hemostatic properties. Incubation purified recombinant with cultured resulted time- and dose-dependent acquisition tissue factor procoagulant activity. Concomitant enhanced activity, also suppressed...
Little is known about the mechanisms converting psychosocial stress into cellular dysfunction. Various genes, up-regulated in atherosclerosis but also by stress, are controlled transcription factor nuclear kappaB (NF-kappaB). Therefore, NF-kappaB a good candidate to convert activation. Volunteers were subjected brief laboratory test and activity was determined peripheral blood mononuclear cells (PBMC), as window body because PBMC play role diseases such atherosclerosis. In 17 of 19...
Activation of the transcription factor nuclear factor-κB (NF-κB) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast short transient activation NF-κB vitro, we observed a long-lasting sustained absence decreased IκBα mononuclear cells from patients with type 1 diabetes. This was associated increased NF-κBp65. A comparable increase NF-κBp65 antigen mRNA also vascular endothelial diabetic rats. As mechanism, propose that binding ligands...
Tumor necrosis factor/cachectin (TNF) has been implicated as a mediator of the host response in sepsis and neoplasia. Recent work shown that TNF can modulate endothelial cell hemostatic properties, suggesting endothelium is target tissue for TNF. This led us to examine whether cells have specific binding sites augment biological by elaborating inflammatory mediator, IL-1. Incubation 125I-recombinant human with confluent, cultured umbilical vein resulted time-dependent, reversible, saturable...
Previous studies demonstrated that endothelial cells participate actively in both anticoagulant and procoagulant reactions. Although mechanisms predominate on the surface of quiescent cells, perturbed can promote coagulation through coordinated induction activity suppression mechanisms. Purified recombinant interleukin 1 was infused intravenously into rabbits coagulant properties native aortic endothelium were subsequently studied. Interleukin infusion resulted a time- dose-dependent...
High-mobility group box-1 (HMGB1) is a nuclear factor released by necrotic cells and activated immune cells. HMGB1 signals via members of the toll-like receptor family for advanced glycation end products (RAGE). Although has been implicated in ischemia/reperfusion (I/R) injury liver lung, its role I/R heart remains unclear.Here, we demonstrate that acts as an early mediator inflammation organ damage heart. levels were already elevated 30 minutes after hypoxia vitro ischemic vivo. Treatment...
The pattern recognition receptor, RAGE (receptor for advanced glycation endproducts), propagates cellular dysfunction in several inflammatory disorders and diabetes. Here we show that functions as an endothelial adhesion receptor promoting leukocyte recruitment. In animal model of thioglycollate-induced acute peritonitis, recruitment was significantly impaired RAGE-deficient mice opposed to wild-type mice. diabetic observed enhanced the inflamed peritoneum compared with nondiabetic mice;...
Abstract High mobility group box 1 (HMGB1) is an abundant and conserved nuclear protein that released by necrotic cells acts in the extracellular environment as a primary proinflammatory signal. In this study we show human dendritic cells, which are specialized Ag presentation to T actively release their own HMGB1 into milieu upon activation. This secreted necessary for up-regulation of CD80, CD83, CD86 surface markers IL-12 production. The also required clonal expansion, survival,...
Meth-A sarcoma cells were stable transfected to overexpress (sense construct) or underexpress (antisense tissue factor. In vitro, there was no difference in plating efficiency growth between these cell lines. vivo, tumor factor grew more rapidly, and established larger vascularized tumors than control transfectants. Antisense transfectants the slowest least vascularized. Anticoagulation of mice with warfarin did not alter Tumor over-expressing released (compared transfectants) mitogenic...
Abstract High‐mobility group box chromosomal protein 1 (HMGB1) is a with both intranuclear functions and extracellular cytokine‐like effects. In this report, we study possible candidate receptors for HMGB1 on macrophages (Mφ) define pathways activated by binding. Bone marrow Mφ were prepared from Dark Agouti (DA) rats stimulated in vitro HMGB1. The kinetics of tumour necrosis factor (TNF) production, NO activation p38 mitogen‐activated kinase (MAPK), p44/42 MAPK‐ SAPK/JNK‐signalling...
While the initiation of adaptive and innate immune response is well understood, less known about cellular mechanisms propagating inflammation. The receptor for advanced glycation end products (RAGE), a transmembrane immunoglobulin superfamily, leads to perpetuated cell activation. Using novel animal models with defective or tissue-specific RAGE expression, we show that in these does not play role response. However, deletion provides protection from lethal effects septic shock caused by cecal...
Binding activity for nuclear factor kappa B (NFkappaB) consensus probes was studied in extracts from peripheral blood mononuclear cells of 15 septic patients (10 surviving and 5 not surviving). Nonsurvivors could be distinguished survivors by an increase NFkappaB binding during the observation period (P < 0.001). The comparable to APACHE-II score as a predictor outcome. Intravenous somatic gene transfer with expression plasmid coding IkappaBalpha used investigate role members family mouse...
While the initiation of adaptive and innate immune response is well understood, less known about cellular mechanisms propagating inflammation. The receptor for advanced glycation end products (RAGE), a transmembrane immunoglobulin superfamily, leads to perpetuated cell activation. Using novel animal models with defective or tissue-specific RAGE expression, we show that in these does not play role response. However, deletion provides protection from lethal effects septic shock caused by cecal...
Damaged mitochondria generate an excess of superoxide, which may mediate tissue injury in diabetes. We hypothesized that diabetic nephropathy, advanced glycation end-products (AGEs) lead to increases cytosolic reactive oxygen species (ROS), facilitate the production mitochondrial superoxide. In normoglycemic conditions, exposure primary renal cells AGEs, transient overexpression receptor for AGEs (RAGE) with adenoviral vector, and infusion healthy rodents each induced oxidative stress, led...
Endothelium is an important target of tumor necrosis factor/cachectin (TNF), a central mediator the host response in endotoxemia and Gram-negative sepsis. In this report, TNF shown to increase permeability endothelial cell monolayers macromolecules lower molecular weight solutes by mechanism involving pertussis toxin-sensitive regulatory G protein. Within 1-3 h exposure (5 nM), changes shape/cytoskeleton occurred that led disruption monolayer continuity with formation intercellular gaps....
In ischemic stroke, the necrotic core is surrounded by a zone of inflammation, in which delayed cell death aggravates initial insult. Here, we provide evidence that receptor for advanced glycation end products (RAGE) functions as sensor and contributes to inflammation brain damage. The RAGE ligand high mobility group box 1 (HMGB1) was elevated serum stroke patients released from tissue mouse model cerebral ischemia. A neutralizing anti-HMGB1 antibody HMGB1 A, an antagonist at RAGE,...