A5072520222- Neonatal Respiratory Health Research
- Immune Response and Inflammation
- Neonatal and Maternal Infections
- Infant Nutrition and Health
- Immune Cell Function and Interaction
- Respiratory viral infections research
- Viral Infections and Immunology Research
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Virus-based gene therapy research
- Signaling Pathways in Disease
- Lipid Membrane Structure and Behavior
- Immune responses and vaccinations
- Influenza Virus Research Studies
- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Sepsis Diagnosis and Treatment
- Erythrocyte Function and Pathophysiology
- Epigenetics and DNA Methylation
- Nanocomposite Films for Food Packaging
- Drug-Induced Hepatotoxicity and Protection
- American Sports and Literature
- Cell death mechanisms and regulation
- Invertebrate Immune Response Mechanisms
- TGF-β signaling in diseases
Universitätsklinikum Aachen
2016-2025
RWTH Aachen University
2010-2021
Boston Children's Hospital
2012-2013
University of Duisburg-Essen
2003-2008
University of Bonn
2002
Max Planck Institute for Metabolism Research
2001
University of Cologne
2001
Universitätsklinikum Knappschaftskrankenhaus Bochum
1999
Ruhr University Bochum
1999
Max Planck Institute of Biochemistry
1994
Regulation of chromatin is an important aspect controlling promoter activity and gene expression. Posttranslational modifications core histones allow proteins associated with transcription to access chromatin. Closely promoters actively transcribed genes, trimethylation histone H3 at lysine 4 (H3K4me3) a mark set by several protein complexes. Some these complexes contain the trithorax ASH2 combined MLL oncoproteins. We identified human in complex oncoprotein MYC. This finding, together...
Abstract Neonatal sepsis is characterized by hyperinflammation causing enhanced morbidity and mortality compared to adults. This suggests differences in the response towards invading threats. Here we investigate activated cord blood macrophages (CBMΦ) comparison adult (PBMΦ), indicating incomplete interferon gamma (IFN-γ) interleukin 10 (IL-10)-induced activation of CBMΦ. CBMΦ show reduced expression phagocytosis receptors cytokine addition altered energy metabolism. In particular, IFN-γ as...
Neonatal sepsis remains a burden problem by showing minimal initial symptoms of subtle character, nonspecific manifestation, and diagnostic pitfalls. The clinical course can be fulminant fatal if treatment is not commenced promptly. It therefore crucial to establish early diagnosis initiate adequate therapy. Besides symptoms, the most reliable laboratory markers in establishing currently combined measurement CRP cytokine (IL-6 IL-8). Due their different kinetics, gap might occur thus...
The plasma membrane contains distinct domains that are characterized by a high concentration of sphingolipids and cholesterol. These microdomains also referred to as rafts, seem be intimately involved in transmembranous signaling often initiate interactions pathogens the host cell membranes. Here, we investigated further reorganization rafts cultured epithelial cells ex vivo isolated nasal after infection with rhinoviruses. We demonstrate formation ceramide-enriched platforms large...
Cellulose nanocrystals (CNCs) are unique and promising natural nanomaterials that can be extracted from native cellulose fibers by acid hydrolysis. In this study, we developed chemically modified CNC derivatives covalent tethering of PEGylated biotin perylenediimide (PDI)-based near-infrared organic dye evaluated their suitability for labeling imaging different cell lines including J774A.1 macrophages, NIH-3T3 fibroblasts, HeLa adenocarcinoma cells, primary murine dendritic cells....
Abstract Neonatal sepsis is accompanied by impaired apoptotic depletion of monocytes and macrophages (MΦ), aberrant cytokine production, cell metabolism, sustained inflammation. Macrophage-colony stimulating factor (M-CSF) triggers the differentiation from into MΦ (MΦ-0). Interleukin-10 (IL10) Interferon-gamma (IFNy) further differentiate subpopulations, anti-inflammatory MΦ-IL10 pro-inflammatory MΦ-IFNy subtype. We previously have shown significant differences between adult (PBMΦ) cord...
Phagocytosis induced cell death (PICD) is crucial for controlling phagocyte effector cells, such as monocytes, at sites of infection, and essentially contributes to termination inflammation. Here we tested the hypothesis, that during PICD bystander apoptosis non-phagocyting monocytes occurs, induction mediated via tumor necrosis factor-alpha (TNF-α TNF-α secretion -signalling causal. Monocytes were infected with Escherichia coli (E. coli), expressing green fluorescent protein (GFP), or a...
ABSTRACT In previous studies we have identified actin rearrangement-inducing factor 1 as an early gene product of Autographa californica multicapsid nuclear polyhedrosis virus that is involved in the remodeling cytoskeleton. We constructed viral recombinants with a mutated Arif-1 open reading frame confirm causal link expression and rearrangement observed accumulation F-actin at plasma membrane 3 to 7 h postinfection. Infection Arif mutant viruses leads loss TN-368 cells, although course...
Rhinoviral infections belong to the most frequent human characterized by common cold, chronic bronchitis, exacerbations of asthma, otitis media and sinusitis. Here, we define molecular mechanisms that mediate epithelial cells with rhinovirus strain 14 (RV14). We demonstrate RV14 activates p38-MAPKinase (p38-K) in a biphasic time course. Early stimulation p38-K was observed few minutes after initiation infection, while late increase activity occurred 7-12 hrs upon infection. The mediated...
Phagocytosis-induced cell death (PICD) is diminished in cord blood monocytes (CBMO) as compared to cells from adults (PBMO) due differences the CD95-pathway. This may support a prolonged pro-inflammatory response with sequels of sustained inflammation seen neonatal sepsis. Here we hypothesized that TNF-α mediated induction apoptosis impaired CBMO TNFR1-dependent internalization. Monocytes were infected Escherichia coli-GFP (E. coli-GFP). Monocyte phenotype, phagocytic activity, apoptosis,...
Background: Cleaving ligands and receptors of the tumor necrosis factor (TNF) superfamily can critically regulate induction apoptosis. Matrix metalloproteinases (MMPs) such as MMP-9 factor-α-converting enzyme (TACE) have been shown to cleave CD95-Ligand (CD95L) TNF/(TNF receptor-1) TNFR1 which induce phagocytosis induced cell death (PICD) in adult monocytes. This process is reduced neonatal Methods: Here we tested vitro, whether Escherichia coli infection mounts for activation TACE monocytes...
Platelet factor 4 (PF4) is a pleiotropic inflammatory chemokine, which has been implicated in various disorders including liver fibrosis. However, its role acute diseases not yet elucidated. Here we describe an unexpected, anti-inflammatory of PF4. Serum concentrations PF4 were measured patients and mice with diseases. Acute injury was induced either by carbon tetrachloride or D-galactosamine hydrochloride lipopolysaccharide. levels decreased PF4-/- displayed increased damage both models...
Immunoglobulins (IVIG) have been shown to be useful in adults suffering from sepsis. In contrast, prophylactic and curative IVIG trials failed show beneficial effects neonates. We tested the hypothesis that IVIG, different on monocytes cord blood (CBMO) peripheral (PBMO) with respect survival, phenotype, function.Mononuclear cells, or purified monocytes, were cultured 5% human serum, incubated polyvalent (1 mg/ml), stimulated green fluorescent protein (GFP)-labeled Escherichia coli (E....
Background Invasive fungal infections with Candida albicans (C. albicans) occur frequently in extremely low birthweight (ELBW) infants and are associated poor outcome. Phagocytosis of C.albicans initializes apoptosis monocytes (phagocytosis induced cell death, PICD). PICD is reduced neonatal cord blood (CBMO). Hypothesis C. causes which differs between (CBMO) adult peripheral (PBMO) due to lower stimulation TLR-mediated immune responses. Methods The ability phagocytose albicans, expression...
Neonates are highly susceptible to microbial infections which is partially attributable fundamental phenotypic and functional differences between effector cells of the adult neonatal immune system. The resolution inflammation essential return tissue homeostasis, but given that various diseases, such as periventricular leukomalacia, necrotizing enterocolitis, or bronchopulmonary dysplasia, characterized by sustained inflammation, newborns seem predisposed a dysregulation inflammatory...
Uptake of bacteria by phagocytes is a crucial step in innate immune defence. Members the disintegrin and metalloproteinase (ADAM) family critically control response limited proteolysis surface expressed mediator molecules. Here, we investigated significance ADAM17 its regulatory adapter molecule iRhom2 for bacterial uptake phagocytes. Inhibition activity led to increased phagocytosis pHrodo labelled Gram-negative -positive (E. coli S. aureus, respectively) human murine monocytic cell lines...