A5075721841- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Cytokine Signaling Pathways and Interactions
- Protein Tyrosine Phosphatases
- interferon and immune responses
- NF-κB Signaling Pathways
- Immune Response and Inflammation
- Pharmacological Effects of Natural Compounds
- Cell Adhesion Molecules Research
- Gene Regulatory Network Analysis
- Protein Kinase Regulation and GTPase Signaling
- RNA Research and Splicing
- Estrogen and related hormone effects
- Bioactive Compounds and Antitumor Agents
- Atherosclerosis and Cardiovascular Diseases
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Chemokine receptors and signaling
- Receptor Mechanisms and Signaling
- Galectins and Cancer Biology
- Medicinal Plant Pharmacodynamics Research
- PI3K/AKT/mTOR signaling in cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Virus-based gene therapy research
- Biomedical and Chemical Research
Otto-von-Guericke University Magdeburg
2012-2022
University Hospital Magdeburg
2010-2022
University Medical Center Groningen
2017
University of Groningen
2017
RWTH Aachen University
2005-2014
GTx (United States)
2011
Universitätsklinikum Aachen
1998-2009
TU Dresden
2008
Charité - Universitätsmedizin Berlin
2004
Praxis für Hämatologie und Onkologie
2003
Interleukin-6 is involved in the regulation of many biological activities such as gene expression, cell proliferation, and differentiation. The control termination cytokine signaling important initiation signal transduction pathways. Three families proteins down-regulation have been described recently: (i) SH2 domain-containing protein-tyrosine phosphatases (SHP), (ii) suppressors (SOCS), (iii) protein inhibitors activated STATs (PIAS). We analyzed interplay two pathway interleukin-6...
Abstract On human macrophages IL-10 acts as a more potent anti-inflammatory cytokine than IL-6, although both cytokines signal mainly via activation of the transcription factor STAT3. In this study we compare and IL-6 signaling in primary derived from blood monocytes. Pretreatment with PMA or proinflammatory mediators LPS TNF-α blocks IL-6-induced STAT3 activation, whereas IL-10-induced remains largely unaffected. Although induces feedback inhibitor suppressor 3 (SOCS3) macrophages,...
Eighty percent of patients newly infected with the hepatitis C virus (HCV) develop chronic infection, suggesting that HCV can effective strategies to escape unspecific and specific immune response host. Because SOCS molecules have been recognized be powerful inhibitors cytokine signaling via Jak/STAT pathway, virus-induced expression these should an efficient instrument counteract cellular toward interferons (IFNs), essential part first line antiviral response. This study shows...
Interleukin-6 (IL-6) activates the Jak/STAT pathway as well mitogen-activated protein kinase cascade. Tyrosine 759 of IL-6 signal-transducing receptor subunit gp130 has been identified being involved in negative regulation IL-6-induced gene induction and activation pathway. Because this site is known to be a recruitment motif for protein-tyrosine phosphatase SHP2, it suggested that SHP2 mediator tyrosine 759-dependent signal attenuation. We recently observed suppressor cytokine-signaling...
Recent findings indicate that cytokine signaling can be modulated by other mediators of simultaneously activated signal transduction pathways. In this study we show LPS and TNFα are potent inhibitors IL‐6‐mediated STAT3 activation in human monocyte derived macrophages, rat liver macrophages RAW 264.7 mouse but not hepatoma cells (HepG2) or hepatocytes. Accordingly, were found to induce the expression SOCS3 mRNA each investigated type HepG2 cells. Using a specific inhibitor, evidence is...
Interleukin-6 is a pleiotropic cytokine with high clinical relevance and an important mediator of cellular communication, orchestrating both pro- anti-inflammatory processes. Interleukin-6-induced signalling initiated by binding IL-6 to the receptor α subsequent signal transducing subunit gp130. This active complex initiates through Janus kinase/signal transducer activator transcription pathway. Of note, exists in soluble transmembrane form. Binding membrane-bound induces classic signalling,...
Gastrointestinal cancers are frequently associated with chronic inflammation and excessive secretion of IL-6 family cytokines, which promote tumorigenesis through persistent activation the GP130/JAK/STAT3 pathway. Although tumor progression can be prevented by genetic ablation Stat3 in mice, this transcription factor remains a challenging therapeutic target paucity clinically approved inhibitors. Here, we uncovered parallel mTOR complex 1 (mTORC1) alongside STAT3 human intestinal-type...
Stimulation of the interleukin-6 (IL-6) signalling pathway occurs via IL-6 receptor–glycoprotein 130 (IL-6R–gp130) receptor complex and results in regulation acute-phase protein genes liver cells. Ligand binding to leads tyrosine phosphorylation activation Janus kinases (Jak), signal transducing subunit gp130, followed by recruitment transducer activator transcription factors STAT3 STAT1 src homology domain (SH2)-containing phosphatase (SHP2). The phosphorylated STAT dissociate from...
Two families of transcription factors mediate interferon (IFN) signaling. The first family, signal transducers and activators (STATs), is activated within minutes IFN treatment. Specific phosphorylation events lead to their translocation the nucleus, formation transcriptional complexes, induction second family termed regulatory (IRFs). Interferon consensus sequence binding protein (ICSBP) a member IRF that expressed only in cells immune system acts as repressor. ICSBP binds DNA through...
The cytokines TNF and IL-6 play a critical role early in liver regeneration following partial hepatectomy (PH). Since activates signal transducers activators of transcription (STATs), we examined whether the suppressors cytokine signaling (SOCS) may be involved terminating signaling. We show here that SOCS-3 mRNA is induced 40-fold 2 hours after surgery. SOCS-2 CIS are only weakly induced, SOCS-1 not detectable. induction PH transient correlates with decrease STAT-3 DNA binding loss tyrosine...
Interferon regularory factor 1 (IRF-1) is a DNA-bindlng which recognizes regulatory elements In the promoters of (IFN)-β and some IFN-Inducible genes. We observed that expression transfected murlne IRF-1 different mammalian cell lines leads to down-regulation or stop proliferation depending on extent expression. Expression fusion proteins composed hormone binding domain human estrogen receptor does not exhibit activity absence estrogen. However, after treatment cells IFN-β are activated...
The potential of some proinflammatory mediators to inhibit gp130-dependent STAT3 activation by enhancing suppressor cytokine signaling (SOCS) 3 expression represents an important molecular mechanism admitting the modulation cellular response toward gp130-mediated signals. Thus, it is necessary understand mechanisms involved in regulation SOCS3 mediators. In this study, we investigate initiated TNF-alpha. contrast IL-6, TNF-alpha increases stabilizing mRNA. Activation MAPK kinase 6...
The inflammatory response involves a complex interplay of different cytokines which act in an auto- or paracrine manner to induce the so-called acute phase response. Cytokines are known crosstalk on multiple levels, for instance by regulating mRNA stability targeted through activation p38-MAPK pathway. In our study we discovered new mechanism that answers long-standing question how pro-inflammatory and environmental stress restrict immediate signalling interleukin (IL)-6-type cytokines. We...
Interleukin (IL)‐6 and IL‐6‐type cytokines signal through the gp130/Jak/STAT transduction pathway. The key components involved are transducing receptor subunit gp130, Janus kinases Jak1, Jak2 Tyk2, STAT1 STAT3 of family transducers activators transcription, protein tyrosine phosphatase SHP2 suppressors cytokine signalling SOCS1, SOCS2 SOCS3. Whereas considerable information has been accumulated concerning time‐course activation for individual molecules, data on availability proteins in...
Interleukin (IL)-6 is a pleiotropic cytokine involved in the differentiation and proliferation of hematopoietic cells. Hepatocytes respond to IL-6 with synthesis secretion acute-phase proteins. In addition, plays role as migration factor vivo. present paper, we studied potential mediate human primary T cells cell-derived cell lines. was found induce only presence extracellular matrix, suggesting cross-talk between IL-6- integrin signal transduction pathways. Furthermore, an gradient required...
Abstract Macrophages contribute to the innate immune response by eliminating bacteria, viral particles, and apoptotic bodies. They develop from circulating monocytes. In case of an infection, monocytes attach endothelial cells blood vessels, migrate along cells, leave circulatory system enter inflammatory tissue, differentiate into macrophages. Cell migration is induced frequently chemokines that act through G-protein-coupled receptors. Only a few cytokines signaling single-transmembrane...
Abstract Cellular communication via intracellular signalling pathways is crucial. Expression and activation of proteins heterogenous between isogenic cells the same cell-type. However, mechanisms evolved to enable sufficient ensure cellular functions. We use information theory clarify facilitating IL-6-induced JAK/STAT despite cell-to-cell variability. show that different enabling robustness against variability complement each other. Early STAT3 robust as long cytokine concentrations are...
Abstract Background Cell-to-cell heterogeneity is an inherent feature of multicellular organisms and central in all physiological pathophysiological processes including cellular signal transduction. The cytokine IL-6 essential mediator pro- anti-inflammatory processes. Dysregulated IL-6-induced intracellular JAK/STAT signalling associated with severe inflammatory proliferative diseases. Under conditions rigorously controlled timely orchestrated by regulatory mechanisms such as expression the...