A5000113493- Immune Response and Inflammation
- Inflammasome and immune disorders
- Acute Kidney Injury Research
- Endometriosis Research and Treatment
- Organ Transplantation Techniques and Outcomes
- Uterine Myomas and Treatments
- Tuberculosis Research and Epidemiology
- Pneumonia and Respiratory Infections
- Heme Oxygenase-1 and Carbon Monoxide
- Chronic Kidney Disease and Diabetes
- Urinary Tract Infections Management
- Urological Disorders and Treatments
- Advanced Glycation End Products research
- Inflammation biomarkers and pathways
- Neonatal Respiratory Health Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Ovarian cancer diagnosis and treatment
- Renal Transplantation Outcomes and Treatments
- Birth, Development, and Health
- Gynecological conditions and treatments
- Escherichia coli research studies
- Renal and related cancers
- Immune cells in cancer
- Transplantation: Methods and Outcomes
- Mesenchymal stem cell research
Máxima Medisch Centrum
2020-2025
Radboud University Nijmegen
2020-2025
Maastricht University
2024
Maastricht University Medical Centre
2024
University of Amsterdam
2012-2023
Amsterdam University Medical Centers
2018-2023
Amsterdam UMC Location University of Amsterdam
2010-2019
University of Iowa
2009
Utrecht University
2002
Dying cells are capable of activating the innate immune system and inducing a sterile inflammatory response. Here, we show that necrotic sensed by Nlrp3 inflammasome resulting in subsequent release proinflammatory cytokine IL-1β. Necrotic produced pressure disruption, hypoxic injury, or complement-mediated damage were inflammasome. activation was triggered part through ATP mitochondria released from damaged cells. Neutrophilic influx into peritoneum response to vivo also markedly diminished...
TLRs are conserved pattern recognition receptors that detect motifs of pathogens and host material released during injury. For unknown reasons, renal TLR2 mRNA is mainly expressed by tubular cells enhanced upon ischemia/reperfusion (I/R) We evaluated the role in I/R injury using TLR2-/- TLR2+/+ mice, antisense oligonucleotides, chimeric mice deficient leukocyte or TLR2. Tubular needed to produce significant cytokine chemokine amounts ischemia vitro. played a proinflammatory detrimental vivo...
Alveolar macrophages (AMs) are considered major effector cells in host defense against respiratory tract infections by virtue of their potent phagocytic properties. In addition, AMs may regulate the inflammatory response to infection production cytokines and capacity phagocytose apoptotic polymorphonuclear (PMNs). To elucidate vivo contribution AM pneumococcal pneumonia, we depleted mice via pulmonary application liposomal dichloromethylene-bisphosphonate (AM- mice) before inoculation with...
ABSTRACT To determine the role of Toll-like receptor 4 (TLR4) in immune response to pneumonia, C3H/HeJ mice (which display a mutant nonfunctional TLR4) and C3H/HeN wild-type were intranasally infected with either Streptococcus pneumoniae (a common gram-positive respiratory pathogen) or Klebsiella gram-negative pathogen). In cases pneumococcal TLR4 showed reduced survival only after infection low-level bacterial doses, which was associated higher burden their lungs 48 h postinfection....
Toll-like receptors (TLRs) can detect endogenous danger molecules released upon tissue injury resulting in the induction of a proinflammatory response. One TLR family members, TLR4, is constitutively expressed at RNA level on renal epithelium and this expression enhanced ischemia/reperfusion (I/R) injury. The functional relevance organ-specific upregulation remains however unknown. We therefore investigated specific role TLR4 relative contribution its two downstream signaling cascades,...
Abstract Mycobacterium tuberculosis bacilli are intracellular organisms that reside in phagosomes of alveolar macrophages (AMs). To determine the vivo role AM depletion host defense against M. infection, mice with pulmonary induced by intranasal administration virulent were treated intranasally either liposome-encapsulated dichloromethylene diphosphonate (AM− mice), liposomes, or saline (AM+ mice). AM− completely protected lethality, which was associated a reduced outgrowth mycobacteria...
Hydrogen sulfide (H(2)S) can induce a hypometabolic, hibernation-like state in mammals when given subtoxic concentrations. Pharmacologically reducing the demand for oxygen is promising strategy to minimize unavoidable hypoxia-induced injury such as ischemia/reperfusion during renal transplantation. Here we show that H(2)S reduces metabolism vivo, ex and vitro. Furthermore, demonstrate beneficial effects of H(2)S-induced hypometabolism model bilateral using three different treatment...
Toll-like receptors (TLRs) can orchestrate an inflammatory response upon activation by pathogen-associated motifs and release of endogenous stress ligands during tissue injury. The kidney constitutively expresses most TLRs, including TLR4. function TLR4 the inflammation, tubular atrophy, fibrosis that accompany progressive renal injury is unknown. Here, we subjected wild-type (WT) TLR4-deficient mice to unilateral ureteral obstruction observed elevated levels mRNA in after obstruction. One...
The innate immune response is important in ventilator-induced lung injury (VILI) but the exact pathways involved are not elucidated. authors studied role of intracellular danger sensor NLRP3 inflammasome.NLRP3 inflammasome gene expression was analyzed respiratory epithelial cells and alveolar macrophages obtained from ventilated patients (n = 40). In addition, wild-type deficient mice were randomized to low tidal volume (approximately 7.5 ml/kg) high 15 ventilation. presence uric acid...
An accumulating body of evidence shows that gut microbiota fulfill an important role in health and disease by modulating local systemic immunity. The importance the microbiome development kidney disease, however, is largely unknown. To study this concept, we depleted with broad-spectrum antibiotics performed renal ischemia-reperfusion (I/R) injury mice. Depletion significantly attenuated damage, dysfunction, remote organ maintained tubular integrity after I/R injury. Gut flora–depleted mice...
Mitochondrial dysfunction is the most prominent source of oxidative stress in acute and chronic kidney disease. NLRX1 a receptor innate immune system that ubiquitously expressed localized mitochondria. We investigated whether may act at interface metabolism immunity model stress. Using chimeric mouse for renal ischemia-reperfusion injury, we found protects against mortality, mitochondrial damage, epithelial cell apoptosis an stress-dependent fashion. regulates phosphorylation integrity,...
The development of active tuberculosis after infection with Mycobacterium is almost invariably caused by a persistent or transient state relative immunodeficiency. Leptin, the product obese (ob) gene, pleiotropic protein produced mainly adipocytes and down-regulated during malnutrition starvation, conditions closely connected tuberculosis. To investigate role leptin in tuberculosis, we intranasally infected wild-type (Wt) leptin-deficient ob/ob mice live virulent M. Ob/ob displayed higher...
Abstract The epidermal growth factor-seven transmembrane (EGF-TM7) family is a group of seven-span receptors predominantly expressed by cells the immune system. Family members CD97, EGF module-containing mucin-like receptor (EMR) 1, EMR2, EMR3, EMR4, and EGF-TM7-latrophilin-related protein are characterized an extended extracellular region with variable number N-terminal EGF-like domains. EGF-TM7 bind cellular ligands as demonstrated interaction CD97 decay accelerating factor (CD55) dermatan...
Tissue fibrosis and chronic inflammation are common causes of progressive organ damage, including renal disease, leading to loss physiological functions. Recently, it was shown that Toll-like receptor 2 (TLR2) is expressed in the kidney activated by endogenous danger signals. The expression function TLR2 during has however not yet been elucidated. Therefore, we studied human murine diseases explored its role inducing obstructive nephropathy TLR2(-/-) or TLR2(+/+) mice. We found markedly...
Recent studies indicate that the innate immune system is not only triggered by exogenous pathogens and pollutants, but also endogenous danger signals released during ischemia necrosis. As triggers for NLRP3 inflammasome protein complex appear to overlap with those cardiac ischemia-reperfusion (I/R) ischemic preconditioning (IPC), we explored possibility involved in IPC acute I/R injury of heart.Baseline performance were investigated isolated, Langendorff-perfused hearts from wild-type (WT),...
TFE -fusion renal cell carcinomas ( RCCs ) are caused by chromosomal translocations that lead to overexpression of the TFEB and TFE3 genes Kauffman et al., 2014 ). The mechanisms leading kidney tumor development remain uncharacterized effective therapies yet be identified. Hence, need model these diseases in an experimental animal system Here, we show kidney-specific transgenic mice, resulted clear cells, multi-layered basement membranes, severe cystic pathology, ultimately papillary with...