A5000999011- Toxic Organic Pollutants Impact
- Skin Protection and Aging
- Carcinogens and Genotoxicity Assessment
- Pharmacogenetics and Drug Metabolism
- Genomics, phytochemicals, and oxidative stress
- Eicosanoids and Hypertension Pharmacology
- Effects and risks of endocrine disrupting chemicals
- Aldose Reductase and Taurine
- Immune cells in cancer
- Air Quality and Health Impacts
- Adipose Tissue and Metabolism
- bioluminescence and chemiluminescence research
- Retinoids in leukemia and cellular processes
- Inflammatory mediators and NSAID effects
- Immune Response and Inflammation
- DNA Repair Mechanisms
- Synthesis and biological activity
- Drug Transport and Resistance Mechanisms
- Crystallization and Solubility Studies
- Psoriasis: Treatment and Pathogenesis
- Cancer, Hypoxia, and Metabolism
- Computational Drug Discovery Methods
- Immune Cell Function and Interaction
- Immunotoxicology and immune responses
- X-ray Diffraction in Crystallography
Leibniz Institute of Environmental Medicine
2016-2025
Nagoya City University
2022
Okazaki City Hospital
2022
Heinrich Heine University Düsseldorf
2006-2015
Institute of Molecular Biology and Biophysics
2014
Leibniz Association
2011
The aryl hydrocarbon receptor (AhR) is involved in the regulation of immune responses, T-cell differentiation, and immunity. Here, we show that inflammatory stimuli such as LPS induce expression AhR human dendritic cells (DC) associated with an AhR-dependent increase CYP1A1 (cytochrome P4501A1). In vivo data confirmed elevated by LPS-enhanced 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated induction thymus B6 mice. Inhibition nuclear factor-κB (NF-κB) repressed both normal LPS-enhanced,...
Abstract The human aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that pivotal regulator of physiology and pathophysiology. Allosteric inhibition AhR was previously thought to be untenable. Here, we identify carvones as noncompetitive, insurmountable antagonists characterize the structural functional consequences their binding. Carvones do not displace radiolabeled ligands from binding but instead bind allosterically within bHLH/PAS-A region AhR. influence...
Because of their lipophilicity, persistent organic pollutants (POPs) cross the human placenta, possibly affecting central nervous system development. Most POPs are known aryl hydrocarbon receptor (AhR) ligands and activators AhR signaling. Therefore, activation has been suggested to cause developmental neurotoxicity (DNT).We studied effects on basic processes brain development in two comparative vitro systems determine whether AhR-activation is underlying mechanism for reported DNT humans.We...
Findings from large epidemiologic studies indicate that there is a link between smoking and extrinsic skin ageing. We previously reported matrix metalloproteinases (MMPs) mediate connective tissue damage in exposed to tobacco smoke extracts. Tobacco contains more than 3800 constituents, including numerous water-insoluble polycyclic aromatic hydrocarbons (PAHs) trigger aryl hydrocarbon receptor (AhR) signalling pathways. To analyse the molecular mechanisms involved smoke-induced ageing, we...
The ubiquitously expressed aryl hydrocarbon receptor (AhR) induces drug metabolizing enzymes as well regulators of cell growth, differentiation and apoptosis. Certain AhR ligands promote atherosclerosis, an age-associated vascular disease. Therefore, we investigated the role in functionality aging. We report a lower pulse wave velocity young old AhR-deficient mice, indicative enhanced vessel elasticity. Moreover, endothelial nitric oxide synthase (eNOS) showed increased activity aortas these...
Ultraviolet B (UVB) radiation induces mutagenic DNA photoproducts, in particular cyclobutane pyrimidine dimers (CPDs), epidermal keratinocytes (KC). To prevent skin carcinogenesis, these photoproducts must be removed by nucleotide excision repair (NER) or apoptosis. Here we report that the UVB-sensitive transcription factor aryl hydrocarbon receptor (AHR) attenuates clearance of UVB-induced CPDs human HaCaT KC and from SKH-1 hairless mice. Subsequent RNA interference inhibitor studies...
The aryl hydrocarbon receptor repressor (AhRR) is a member of the (AhR) signaling cascade, which mediates dioxin toxicity and involved in regulation cell growth differentiation. AhRR was described as feedback modulator, counteracts AhR-dependent gene expression. We investigated molecular mechanisms transcriptional human <i>AhRR</i> by cloning its regulatory DNA region located intron I <i>AhRR</i>. By means reporter analyses generation deletion variants, we identified functional,...
There is no doubt that ultraviolet radiation (UVR) contributes to the generation of acquired lentigines in human skin, as indicated by term solar lentigo. A growing number recent epidemiological and mechanistic studies, however, strongly suggest addition UVR, other environmental factors contribute lentigines' formation well. We therefore here introduce 'environment-induced lentigo' (EIL) refer pigment spots skin. In this view point, we (i) summarize existing evidence support a role toxicants...
Abstract As a sensor of polyaromatic chemicals the aryl hydrocarbon receptor (AhR) exerts an important role in immune regulation besides its requirement for xenobiotic metabolism. Transcriptional activation AhR target genes is counterregulated by repressor (AhRR) but exact function AhRR vivo currently unknown. We here show that predominantly expressed cells skin and intestine, different from other genes. Whereas antagonizes anti-inflammatory context systemic endotoxin shock, act concert to...
Background:The aryl hydrocarbon receptor repressor (AhRR) is known to repress (AhR) signaling, but very little regarding the role of AhRR in vivo.Objective:This study tested vivo overexpressing mice on molecular and toxic end points mediated through a prototypical AhR ligand.Methods:We generated AhRR-transgenic (AhRR Tg) based genetic background C57BL/6J wild type (wt) mice. We effect ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) expression cytochrome P450 (CYP)1A1 cytokines various...
Background: The superior therapeutic benefit of clozapine is often associated with metabolic disruptions as obesity, insulin resistance, tachycardia, higher blood pressure, and even hypertension. Aims: These adverse vascular/ events under are similar to those caused by polycyclic aromatic hydrocarbons (PAHs), shows structural similarity well-known ligands the aryl hydrocarbon receptor (AhR). Therefore, we speculated that side effects might rely on AhR signaling. Methods: We examined...