A5017227221- Immune Response and Inflammation
- Sepsis Diagnosis and Treatment
- Immune Cell Function and Interaction
- Inflammation biomarkers and pathways
- Dermatology and Skin Diseases
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Adrenal Hormones and Disorders
- Immune cells in cancer
- Toxic Organic Pollutants Impact
- Skin Protection and Aging
- Cancer, Hypoxia, and Metabolism
- Cytokine Signaling Pathways and Interactions
- Inflammasome and immune disorders
- Chemokine receptors and signaling
- interferon and immune responses
- Metabolomics and Mass Spectrometry Studies
- Adipose Tissue and Metabolism
- Air Quality and Health Impacts
- Neuroinflammation and Neurodegeneration Mechanisms
- Urticaria and Related Conditions
- Contact Dermatitis and Allergies
- Mycotoxins in Agriculture and Food
- Effects and risks of endocrine disrupting chemicals
- Psoriasis: Treatment and Pathogenesis
University of Bonn
2016-2025
Leibniz Institute of Environmental Medicine
2010-2024
Peter Doherty Institute
2023
The University of Melbourne
2023
Odense University Hospital
2017
Heinrich Heine University Düsseldorf
2007-2012
Technical University of Munich
2000-2010
Klinikum rechts der Isar
1999-2007
Ludwig-Maximilians-Universität München
2005
Institute of Medical Microbiology and Hygiene
1999
Psoriasis is an autoinflammatory skin disease of unknown etiology. Topical application Aldara cream containing the Toll-like receptor (TLR)7 agonist Imiquimod (IMQ) onto patients induces flares psoriasis. Likewise, in mice IMQ triggers pathological changes closely resembling psoriatic plaque formation. Key cytokines like IL-23 and type-I IFN (IFN-I), both being produced mainly by dendritic cells (DCs), have been implicated Although plasmacytoid DCs (pDCs) are main source IFNα thought to...
In view of the steadily increasing use zinc oxide nanoparticles in various industrial and consumer applications, toxicological investigations to evaluate their safety are highly justified. We have investigated mechanisms ZnO nanoparticle-induced apoptosis necrosis macrophages relation important role clearance inhaled particulates regulation immune responses during inflammation. murine macrophage RAW 264.7 cell line, treatment caused a rapid induction nuclear condensation, DNA fragmentation,...
The Gi protein-coupled receptor GPR84, which is activated by (hydroxy)fatty acids, highly expressed on immune cells. Recently, 3,3'-diindolylmethane was identified as a heterocyclic, nonlipid-like GPR84 agonist. We synthesized broad range of diindolylmethane derivatives condensation indoles with formaldehyde in water under microwave irradiation. products were evaluated at the human cAMP and β-arrestin assays. Structure-activity relationships (SARs) steep. 3,3'-Diindolylmethanes bearing small...
Abstract TLRs are important sensors of the innate immune system that serve to identify conserved microbial components mount a protective response. They furthermore control survival challenged cell by governing induction pro- and antiapoptotic signaling pathways. Pathogenic Yersinia spp. uncouple balance life death signals in infected macrophages, which compels macrophage undergo apoptosis. The initiation apoptosis infection specifically involves TLR4 signaling, although can activate TLR2...
Recent reports support the concept that major defect in polymicrobial sepsis is an impaired immunologic response to infection. Oligodeoxynucleotides containing CpG sequence motifs (CpG-ODN) were previously shown induce immune protection models of chronic infection with intracellular bacteria, parasites, and viruses due their ability augment IFN-gamma-dependent Th1 responses. Here, we demonstrate challenging mice CpG-ODN substantially increases resistance against acute sepsis. Systemic levels...
Abstract Toll-like receptors (TLRs) are important for the activation of innate immune cells upon encounter microbial pathogens. The present study investigated potential roles TLR2, TLR4, and signaling protein myeloid differentiation factor 88 (MyD88) in polymicrobial septic peritonitis. Whereas both TLR2 TLR4 were dispensable host defense against peritonitis, MyD88-deficient mice protected this infection model. Recruitment neutrophils to focus bacterial clearance normal mice. In contrast,...
Abstract Dendritic cell activation by Toll‐like receptors (TLR) is crucial for the generation of protective immune responses. In addition to common myeloid differentiation factor 88 (MyD88)‐dependent signaling pathway, TLR4 engages adaptor protein Toll/IL‐1 receptor (TIR)‐domain‐containing inducing IFN‐β (TRIF), leading interferon regulatory 3 (IRF‐3) and type I production. Using microarray expression profiling we now identify TRIF as a major regulator TLR4‐triggered program dendritic cells....
Dendritic cells(DCs) are important sentinels of the immune system and frequently reside in areas low oxygen availability, particular course inflammatory processes. Hypoxia-inducible transcription factor (HIF)1α is responsible for major alterations gene expression as part cellular adaptation to concentration. In this study, we generated mice with a conditional deletion HIF1α DCs. Bone marrow-derived DCs from WT mutant expressed elevated levels histocompatibility complex class II CD86 when...
Summary Genetically determined responsiveness to microbial stimuli such as lipopolysaccharide (LPS) may affect the pathophysiology of human sepsis. The D299G mutation in Toll‐like receptor‐4 (TLR4) impairs LPS signalling homozygous and heterozygous individuals. To investigate whether presence TLR4(D299G) correlate with development or outcome sepsis following major visceral surgery was analysed 307 Caucasian patients (154 without 153 sepsis). Sepsis caused 84% by polymicrobial infection....
The aryl hydrocarbon receptor (AHR) regulates the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AHR repressor (AHRR) is an target gene and functions as a ligand-induced AHR; however, its mechanism inhibition controversial. Recently, we reported that TCDD-inducible poly (ADP-ribose) polymerase (TiPARP; ARTD14) also acts AHR, representing new player in action. Here compared ability AHRR- TiPARP-mediated activity. TCDD increased AHRR mRNA levels recruitment to cytochrome P450 1A1...
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...
A diet rich in vegetables and fruit is generally considered healthy because of a high content phytochemicals, vitamins, fiber. The phytochemical indole-3-carbinol (I3C), derivative glucobrassicin, sold as dietary supplement promising diverse health benefits. I3C metabolites act ligands the aryl hydrocarbon receptor (AhR), an important sensor for environmental polyaromatic chemicals. Here, we investigated how AhR ligand supplementation influences target gene expression intestinal microbiota...
A high fat Western-style diet leads to hepatic steatosis that can progress steatohepatitis and ultimately cirrhosis or liver cancer. The mechanism the development of upon nutritional overload is complex only partially understood. Using click chemistry-based metabolic tracing microscopy, we study interaction between Kupffer cells hepatocytes ex vivo. In early phase steatosis, alone do not display significant deviations in fatty acid metabolism. However, co-cultures supernatant transfer...
Abstract Intra-abdominal infection in patients following major visceral surgery is associated with high mortality. Using a macrophage depletion technique, we demonstrate that murine septic peritonitis, Kupffer cells are source of systemic IL-10 levels. cell-depleted mice were highly susceptible to the lethal effects peritonitis and exhibited an increased bacterial load. protected by administration IL-10-Fc fusion protein. Loss cell-derived was weak increase serum IL-12 levels, whereas TNF,...
Abstract IL-22 is a recently discovered cytokine of the IL-10 family that binds to class II receptor composed IL-22R1 and IL-10R2c influences variety immune reactions. As has also been shown modulate cell cycle proliferation mediators such as ERK1/2 JNK, we studied role in proliferation, apoptosis, regulation EMT6 murine breast cancer cells vitro vivo. In this study, report express functional IL-22R indicated by RT-PCR studies, immunoblotting, STAT3 activation assays. Importantly, exposure...
Systemic levels of the key immune regulatory cytokines IL-12 and IL-18 were measured over time in 66 patients with postoperative sepsis (38 survivors 28 nonsurvivors). Sepsis mortality was not significantly associated any clinical parameters examined, including age, gender, underlying disease, surgical procedure. Analysis cytokine showed that during entire observation period, reduced compared control without sepsis. serum did differ between nonsurvivors. In contrast to IL-12, higher both...
Interleukin-22 (IL-22) is a recently discovered proinflammatory cytokine, structurally related to IL-10. Since IL-22 induced by lipopolysaccharide in vivo, we studied the role of model polymicrobial peritonitis. Quantitative real-time reverse transcription-PCR analysis showed marked induction and receptor spleen kidney during course sepsis. The biological activity modulated IL-22-binding protein (IL-22BP), which considered natural antagonist IL-22. To further analyze septic peritonitis, mice...