A5023508681- Acute Kidney Injury Research
- Immune Response and Inflammation
- Urinary Tract Infections Management
- Inflammasome and immune disorders
- Advanced Glycation End Products research
- Proteoglycans and glycosaminoglycans research
- Escherichia coli research studies
- Urinary Bladder and Prostate Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Organ Transplantation Techniques and Outcomes
- Mesenchymal stem cell research
- Chemokine receptors and signaling
- Chronic Kidney Disease and Diabetes
- Tissue Engineering and Regenerative Medicine
- Extracellular vesicles in disease
- Blood Coagulation and Thrombosis Mechanisms
- Heme Oxygenase-1 and Carbon Monoxide
- Poisoning and overdose treatments
- Immune cells in cancer
- Renal Transplantation Outcomes and Treatments
- S100 Proteins and Annexins
- Inflammation biomarkers and pathways
- Cell Adhesion Molecules Research
- Renal and related cancers
- Disaster Response and Management
Amsterdam University Medical Centers
2020
Amsterdam UMC Location University of Amsterdam
2009-2019
University of Amsterdam
2006-2016
Erasmus Hospital
2007
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...
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,...
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...
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,...
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...
Chemokines are important players in the migration of leukocytes to sites injury and also involved angiogenesis, development wound healing. In this study, we performed microarray analyses identify chemokines that play a role during inflammatory repair phase after renal ischemia/reperfusion (I/R) investigated temporal relationship between chemokine expression, leukocyte accumulation damage/repair. C57Bl/6 mice were subjected unilateral ischemia for 45 min sacrificed 3 h, 1 day 7 days...
Podocytes of the kidney adhere tightly to underlying glomerular basement membrane (GBM) in order maintain a functional filtration barrier. The clinical importance podocyte binding GBM via an integrin-laminin-actin axis has been illustrated models with altered function α3β1 integrin, integrin-linked kinase, laminin-521, and α-actinin 4. Here we expanded on podocyte-GBM model by showing that main adhesion receptor, integrin α3β1, interacts tetraspanin CD151 situ humans. Deletion Cd151 mouse...
Progressive renal disease is characterized by tubulo-interstitial injury with ongoing inflammation and fibrosis. The Nlrp3 inflammasome contributes to these pathophysiological processes through its canonical effects in cytokine maturation. may additionally exert inflammasome-independent following tissue injury. Hence, this study we investigated potential non-canonical of progressive subjecting WT Nlrp3-deficient (−/−) mice unilateral ureter obstruction (UUO). Our results revealed a increase...
The chemokine stromal cell-derived factor-1 (SDF-1) is thought to be involved in mediating tissue repair by promoting migration of bone marrow stem or progenitor cells the site injury. Increased levels renal SDF-1 are found after kidney However, recently, we showed that does not play an important role haematopoietic post-ischaemic kidney. function increased expression modulating ischaemia/reperfusion injury remains, therefore, unknown.We studied locally decreasing and subsequent signalling...
The role that the enterococcal surface protein Esp plays in capacity of Enterococcus faecium to adhere uroepithelial cells and it urinary tract infection peritonitis was investigated vitro vivo, respectively, using Esp-expressing E. (E1162) its isogenic Esp-deficient mutant (E1162 Delta esp). expression enhanced binding bladder kidney epithelial cells. In mice, higher numbers E1162 were cultured from kidneys bladders after induction infection, compared with esp numbers. This accompanied by a...
Ischemia reperfusion injury is a common cause of acute kidney and characterized by tubular damage. Mitochondrial DNA released upon severe tissue can act as damage-associated molecular pattern via the innate immune receptor TLR9. Here, we investigated role TLR9 in context moderate or renal ischemia using wild-type C57BL/6 mice TLR9KO mice. Moderate induced dysfunction but did not decrease animal well-being was regulated In contrast, decreased survival after respectively one five days...
Abstract Objective EMR2 and CD97 are closely related members of the epidermal growth factor (EGF)–TM7 family adhesion class 7‐span transmembrane (TM7) receptors. Chondroitin sulfates (CS) have recently been identified as ligands for CD97. CS implicated in pathogenesis rheumatoid arthritis (RA). We undertook this study to determine expression distribution within RA synovial tissue (ST). Methods ST samples were obtained by arthroscopy from 19 patients with RA, 13 inflammatory osteoarthritis...
Abstract Escherichia coli is the most common pathogen found in urinary tract infections (UTIs), mainly affecting children and women. We report that CD44, a hyaluronic acid (HA) binding protein mediates cell-cell cell-matrix interactions, facilitates interaction of E. with urothelial cells thus infection host. CD44 constitutively expressed on HA accumulates coli-induced UTI. In CD44-deficient mice, bacterial outgrowth was dramatically less compared wild-type mice despite similar granulocyte...
Activation of Rap1 by exchange protein activated cAMP (Epac) promotes cell adhesion and actin cytoskeletal polarization. Pharmacologic activation Epac-Rap signaling the Epac-selective analog 8-pCPT-2'-O-Me-cAMP during ischemia-reperfusion (IR) injury reduces renal failure application survival exposure to nephrotoxicant cisplatin. Here, we found that Epac reduced production reactive oxygen species reoxygenation after hypoxia decreasing mitochondrial superoxide production. prevented disruption...
Abstract Renal ischemia reperfusion (IR)-injury induces activation of innate immune response which sustains renal injury and contributes to the development delayed graft function (DGF). Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pro-inflammatory evolutionary conserved pattern recognition variety cells. TREM-1 expression increases following acute chronic injury. However, in IR still unclear. Here, we investigated murine model using different inhibitors: LP17, LR12 fusion...
ABSTRACT Our immune system has to constantly strike a balance between activation and inhibition of an inflammatory response combat invading pathogens avoid inflammation-induced collateral tissue damage. Toll interleukin-1 receptor 8 (IL-1R-8)/single Ig domain IL-1R-related molecule (TIR8/SIGIRR) is inhibitor Toll-like (TLR)/IL-1R signaling, which predominantly expressed in the kidney. The biological role renal TIR8 during infection is, however, unknown. We therefore evaluated expression...
Abstract Lipid accumulation is associated with various forms of acute renal injury; however, the causative factors and pathways underpinning this lipid have not been thoroughly investigated. In study, we performed lipidomic profiling tissue following ischaemia–reperfusion injury (IRI). We identified a significant cholesterol specific phospholipids sphingolipids in kidneys 24 h after IRI. light these findings, hypothesised that involved metabolism may also be altered. Through analysis...