A5003072830- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Hormonal Regulation and Hypertension
- Estrogen and related hormone effects
- Immune Response and Inflammation
- Adrenal Hormones and Disorders
- Cytokine Signaling Pathways and Interactions
- Stress Responses and Cortisol
- Multiple Sclerosis Research Studies
- Reproductive System and Pregnancy
- Hematopoietic Stem Cell Transplantation
- Neuroinflammation and Neurodegeneration Mechanisms
- Mesenchymal stem cell research
- CAR-T cell therapy research
- Asthma and respiratory diseases
- Systemic Lupus Erythematosus Research
- Neuroendocrine regulation and behavior
- NF-κB Signaling Pathways
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- IL-33, ST2, and ILC Pathways
- Testicular diseases and treatments
- Diabetes and associated disorders
University of Göttingen
2014-2025
Universitätsmedizin Göttingen
2015-2024
Nephrologisches Zentrum Goettingen
2019
Hertie Foundation
2014
University of Würzburg
2004-2013
Heidelberg University
1996-2012
University Medical Center Utrecht
2012
University Hospital Heidelberg
2001-2012
German Cancer Research Center
1996-2005
Martha-Maria Hospital
2005
In mammals, circadian oscillators reside not only in the suprachiasmatic nucleus of brain, which harbors central pacemaker, but also most peripheral tissues. Here, we show that glucocorticoid hormone analog dexamethasone induces gene expression cultured rat-1 fibroblasts and transiently changes phase liver, kidney, heart. However, does affect cyclic neurons nucleus. This enabled us to establish an apparent phase-shift response curve specifically for clocks intact animals. contrast clock,...
Transcriptional regulation by the glucocorticoid receptor (GR) is essential for survival. Since GR can influence transcription both through DNA-binding-dependent and -independent mechanisms, we attempted to assess their relative importance in vivo. In order separate these modes of action, introduced point mutation A458T into gene targeting using Cre/loxP system. This impairs dimerization therefore GRE-dependent transactivation while functions that require cross-talk with other factors, such...
The muscle specific ubiquitin E3 ligase MuRF1 has been implicated as a key regulator of atrophy under variety conditions, such during synthetic glucocorticoid treatment. FOXO class transcription factors have proposed important regulators expression, but its regulation by glucocorticoids is not well understood. promoter contains near-perfect palindromic response element (GRE) 200 base pairs upstream the start site. GRE highly conserved in mouse, rat, and human genes along with directly...
Safe and effective cell delivery remains one of the main challenges in cell-based therapy neurodegenerative disorders. Graft survival, sufficient enrichment therapeutic cells brain, avoidance their distribution throughout peripheral organs are greatly influenced by method delivery. Here we demonstrate for first time noninvasive intranasal (IN) mesenchymal stem (MSCs) to brains unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. IN application (INA) MSCs resulted appearance olfactory bulb,...
Anton Bauer, Francois Tronche, Oliver Wessely, Christoph Kellendonk, Holger M. Reichardt, Peter Steinlein, Günther Schütz, and Hartmut Beug Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria; Biology the Cell I, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
Activation of central glucocorticoid receptors caused by the stress that is associated with a learning task facilitates storage acquired information. The molecular mechanism underlying this phenomenon entirely unknown. Glucocorticoid can influence transcription both through DNA binding-dependent and -independent mechanisms. To assess importance these two modes action for spatial memory, we here used male mutant mice in which homodimerization binding receptor largely prevented (GR dim/dim )...
Corticosteroid action in the brain is mediated by mineralocorticoid (MR) and glucocorticoid (GR) receptor. Disturbances MR- GR-mediated effects are thought to impair cognition, behavior, endocrine control. To assess function of limbic MR these processes, we inactivated gene forebrain mouse using Cre/loxP-recombination system. We screened mice with a deficiency various learning exploration tests. The mutant show impaired water-maze task deficits measures working memory on radial maze due...
Glucocorticoids (GCs) are widely used in the treatment of allergic skin conditions despite having numerous side effects. Here we use Cre/loxP-engineered tissue- and cell-specific function-selective GC receptor (GR) mutant mice to identify responsive cell types molecular mechanisms underlying antiinflammatory activity GCs contact hypersensitivity (CHS). CHS was repressed by only at challenge phase, i.e., during reexposure hapten. Inactivation GR gene keratinocytes or T cells did not attenuate...
Summary Glucocorticoids (GCs) are involved in the modulation of macrophage function and thereby control host's immune responses to pathogens. However, neither role hormone concentration nor differential contribution glucocorticoid (GR) mineralocorticoid receptors (MR) these activities known. Here we show that low levels corticosterone enhance NO production as well mRNA expression pro‐inflammatory cytokines, chemokines enzymes required for mediator synthesis. In contrast, at high...
Targeted mutagenesis of the glucocorticoid receptor has revealed an essential function for survival and regulation multiple physiological processes. To investigate effects increased gene dosage receptor, we have generated transgenic mice carrying two additional copies by using a yeast artificial chromosome. Interestingly, overexpression alters basal hypothalamo-pituitary-adrenal axis, resulting in reduced expression corticotropin-releasing hormone adrenocorticotrope fourfold reduction level...
The glucocorticoid receptor (GR) mediates the biological effects of glucocorticoids (GCs) through activation or repression gene expression, either by DNA binding via interaction with other transcription factors, such as AP-1. Work in tissue culture cells on regulation AP-1–dependent genes, collagenase (MMP-13) and stromelysin (MMP-3) has suggested that antitumor antiinflammatory activity GCs is mediated, at least part, GR-mediated downmodulation Here, we have identified phorbol ester-induced...
Abstract High-dose glucocorticoid (GC) therapy is widely used to treat multiple sclerosis (MS), but the underlying mechanisms remain debatable. In this study, we investigated impact of GC administration on experimental autoimmune encephalomyelitis using different receptor (GR)-deficient mutants. Heterozygous GR knockout mice were less sensitive dexamethasone therapy, indicating that expression level determines therapeutic efficacy. Mice reconstituted with homozygous fetal liver cells showed...
Currently, tools to generate loss-of-function mutations in rats are limited. Therefore, we have developed a lentiviral single-vector system for the temporal control of ubiquitous shRNA expression. Here, report transgenic carrying an insulin receptor-specific transcribed from regulatable promoter and identified by concomitant EGFP In absence inducer doxycycline (Dox), observed no siRNA However, Dox treatment at very low concentrations led rapid induction ablation INSR protein As anticipated,...
Sepsis is controlled by endogenous glucocorticoids (GCs). Previous studies provided evidence that crosstalk of the monomeric GC receptor (GR) with proinflammatory transcription factors crucial mechanism underlying suppressive effect. Here we demonstrate mice a dimerization-deficient GR (GRdim) are highly susceptible to sepsis in 2 different models, namely cecal ligation and puncture lipopolysaccharide (LPS)-induced septic shock. TNF-α normally regulated these mice, but down-regulation IL-6...
Abstract Acute lung injury (ALI) is a severe inflammatory disease for which no specific treatment exists. As glucocorticoids have potent immunosuppressive effects, their application in ALI currently being tested clinical trials. However, the benefits of this type regimen remain unclear. Here we identify mechanism glucocorticoid action that challenges long-standing dogma cytokine repression by receptor. Contrarily, synergistic gene induction sphingosine kinase 1 ( SphK1 ) and pro-inflammatory...
Abstract Objective HLA–B27 predisposes to spondylarthritis by an unknown mechanism. A logical candidate mechanism is through recognition of B27 CD8+ T cells. The purpose this study was examine the effects a lack CD8 on that develops in B27/human β 2 ‐microglobulin (Huβ m)–transgenic rats. Methods missense mutation CD8a gene causes loss CD8α expression identified offspring male Sprague‐Dawley rat had been treated with mutagen N ‐ethyl‐ ‐nitrosourea. crossed into B27/Huβ m‐transgenic lines...
Glucocorticoids (GCs) are important regulators of skeletal muscle mass, and prolonged exposure will induce significant atrophy. To better understand the mechanism atrophy induced by elevated GC levels, we examined three different models: exogenous synthetic treatment [dexamethasone (DEX)], nutritional deprivation, denervation. Specifically, tested direct contribution glucocorticoid receptor (GR) in creating a muscle-specific GR-knockout mouse line (MGR e3 KO) using Cre-lox technology. In MGR...
T cell activation is an energy-demanding process fueled by increased glucose consumption and accompanied upregulation of the insulin receptor (INSR). In this article, we report that silencing INSR in inducible knockdown rats impairs selective functions but not thymocyte development. Glucose transport glycolysis activated CD4+ cells were compromised absence INSR, which was associated with alterations intracellular signaling pathways. The observed metabolic defects coincided reduced cytokine...