A5061887105- Immune Response and Inflammation
- Cell death mechanisms and regulation
- interferon and immune responses
- NF-κB Signaling Pathways
- Cytokine Signaling Pathways and Interactions
- Inflammasome and immune disorders
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- Osteoarthritis Treatment and Mechanisms
- Cell Adhesion Molecules Research
- Viral Infections and Vectors
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Nitric Oxide and Endothelin Effects
- Virus-based gene therapy research
- Nuclear Structure and Function
- Cancer-related Molecular Pathways
- Pancreatic function and diabetes
- Microtubule and mitosis dynamics
- Bartonella species infections research
- Autoimmune and Inflammatory Disorders Research
- Helicobacter pylori-related gastroenterology studies
VIB-UGent Center for Inflammation Research
2014-2024
Ghent University
2014-2024
Sapporo Medical University
2016-2024
National Center For Child Health and Development
2020-2022
Cancer Research Institute Ghent
2022
Vlaams Instituut voor Biotechnologie
1995-2012
Radboud University Medical Center
2002-2011
Radboud University Nijmegen
2002-2011
Ghent University Hospital
1996-2011
Matsumoto Dental University
2005-2009
Necrostatin-1 (Nec-1) is widely used in disease models to examine the contribution of receptor-interacting protein kinase (RIPK) 1 cell death and inflammation. We studied three Nec-1 analogs: Nec-1, active inhibitor RIPK1, inactive (Nec-1i), its variant, stable (Nec-1s), more variant. report that identical methyl-thiohydantoin-tryptophan, an potent immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). Both Nec-1i inhibited human IDO, but Nec-1s did not, as predicted by molecular...
p63 inhibits metastasis. Here, we show that (both TAp63 and ΔNp63 isoforms) regulates expression of miR-205 in prostate cancer (PCa) cells, is essential for the inhibitory effects on markers epithelial-mesenchymal transition (EMT), such as ZEB1 vimentin. Correspondingly, effect EMT cell migration reverted by anti-miR-205. p53 mutants inhibit both miR-205, migration, a line expressing endogenous mutated p53, can be abrogated pre-miR-205 or silencing p53. In accordance with this vitro data,...
Highlights•ZEB2 is highly expressed across the macrophage lineage•ZEB2 preserves tissue-specific identities of macrophages tissues•ZEB2 deficient are outcompeted by WT counterparts•LXRα crucial for Kupffer cell identity and maintained ZEB2SummaryHeterogeneity between different populations has become a defining feature this lineage. However, conserved factors remain largely unknown. The transcription factor ZEB2 best described its role in epithelial to mesenchymal transition; however, within...
Abstract Objective Wnt signaling pathway proteins are involved in embryonic development of cartilage and bone, and, interestingly, developmental processes appear to be recapitulated osteoarthritic (OA) cartilage. The present study was undertaken characterize the expression pattern Fz genes during experimental OA determine function selected human OA. Methods Longitudinal analysis performed 2 models Levels messenger RNA for from Wnt/β‐catenin were determined synovium cartilage, results...
In human cells, the RIPK1-RIPK3-MLKL-PGAM5-Drp1 axis drives tumor necrosis factor (TNF)-induced necroptosis through mitochondrial fission, but whether this pathway is conserved among mammals not known. To answer question, we analyzed presence and functionality of reported necroptotic in mice. As humans, knockdown receptor-interacting kinase-3 (RIPK3) or mixed lineage kinase domain like (MLKL) blocks TNF-induced L929 fibrosarcoma cells. However, repression either these proteins did protect...
Tumor necrosis factor (TNF) has very potent antitumor activity, but it also provokes a systemic inflammatory response syndrome that leads to shock, organ failure, and death. Here, we demonstrate interleukin (IL)-17, proinflammatory cytokine known be produced mainly by activated T cells, critical role in this process. Antiserum against IL-17 or deletion of Il17r protected mice lethal TNF challenge. Serum levels TNF-induced IL-6 nitric oxide metabolites were significantly reduced deficient the...
Rationale: Sepsis is one of the leading causes death around world. The failure clinical trials to treat sepsis demonstrates that molecular mechanisms are multiple and still insufficiently understood.Objectives: To clarify long disputed hierarchical contribution several central inflammatory mediators (IL-1β, IL-18, caspase [CASP] 7, CASP1, CASP11) in septic shock explore their therapeutic potential.Methods: LPS- tumor necrosis factor (TNF)-induced lethal shock, cecal ligation puncture (CLP)...
Tumor necrosis factor (TNF) is a central mediator of number important pathologies such as the systemic inflammatory response syndrome. Administration high TNF doses induces acute anorexia, metabolic derangement, inflammation, and eventually shock death. The in vivo effects are largely mediated by complex network TNF-induced cytokines hormones acting together or antagonistically. Since also leptin, hormone secreted adipocytes that modulates food intake metabolism, we questioned role leptin...
Necroptosis contributes to the pathophysiology of several inflammatory, infectious and degenerative disorders. TNF-induced necroptosis involves activation receptor-interacting protein kinases 1 3 (RIPK1/3) in a necrosome complex, eventually leading phosphorylation relocation mixed lineage kinase domain like (MLKL). Using high-content screening small compounds FDA-approved drug libraries, we identified anti-cancer Sorafenib tosylate as potent inhibitor TNF-dependent necroptosis....
TNF is an important mediator in numerous inflammatory diseases, e.g., bowel diseases (IBDs). In IBD, acute increases production can lead to disease flares. Glucocorticoids (GCs), which are steroids that bind and activate the glucocorticoid receptor (GR), able protect animals humans against TNF-induced symptoms. Mice with a poor transcriptional response of GR dimer–dependent target genes were studied model lethal inflammation. contrast GRWT/WT mice, these GRdim/dim mice displayed substantial...
Clostridium difficile is the leading cause of pseudomembranous colitis in hospitalized patients. C. enterotoxins TcdA and TcdB promote this inflammatory condition via a cytotoxic response on intestinal epithelial cells (IECs), but underlying mechanisms are incompletely understood. Additionally, engage Pyrin inflammasome macrophages, whether modulates CDI pathophysiology unknown. Here we show that not functional IECs signaling dispensable for CDI-associated IEC death vivo pathogenesis....
Abstract Background High levels of foreign gene expression in mouse hepatocytes can be achieved by rapid tail vein injection a large volume naked DNA solution, the ‘hydrodynamics‐based procedure’. Rats are more tolerant frequent phlebotomies required for monitoring blood parameters than mice, and thus better some biomedical research. Methods We tested this technique delivery therapeutic protein normal rats, using rat erythropoietin (Epo) plasmid vector, pCAGGS‐Epo. Results obtained maximal...
ABSTRACT Bartonella quintana is a gram-negative microorganism that causes trench fever and chronic bacteremia. B. lipopolysaccharide (LPS) was unable to induce the production of proinflammatory cytokines in human monocytes. Interestingly, LPS potent antagonist Toll-like receptor 4 (TLR4), as it inhibited both mRNA transcription release tumor necrosis factor alpha, interleukin 1β (IL-1β), IL-6 by Escherichia coli monocytes, at ratios ranging from 1,000:1 10:1 ( E. LPS). Likewise, blocked...
The HECT domain E3 ligase HACE1 has been identified as a tumor suppressor in multiple cancers. Here, we report that is central gatekeeper of TNFR1-induced cell fate. Genetic inactivation inhibits TNF-stimulated NF-κB activation and TNFR1-NF-κB-dependent pathogen clearance vivo. Moreover, TNF-induced apoptosis was impaired hace1 mutant cells knockout mice Mechanistically, essential for the ubiquitylation adaptor protein TRAF2 formation apoptotic caspase-8 effector complex. Intriguingly, loss...
Abstract The Aurora kinase family (Aurora A, B and C) are crucial regulators of several mitotic events, including cytokinesis. Increased expression these kinases is associated with tumorigenesis compounds targeting under evaluation in clinical trials (a.o. AT9283, AZD1152, Danusertib, MLN8054). Here, we demonstrate that the pan-Aurora inhibitor Tozasertib (VX-680 MK-0457) not only causes cytokinesis defects through inhibition, but also a potent necroptosis, cell death process regulated...
Receptor interacting protein kinase 1 (RIPK1) plays a crucial role in tumor necrosis factor (TNF)-induced necroptosis, suggesting that this pathway might be druggable. Most inhibitors of RIPK1 are classified as either type II or III inhibitors. This opened up some interesting perspectives for the discovery novel target active site RIPK1. Tozasertib, I pan-aurora (AurK) inhibitor, was found to show very high affinity Because tozasertib presents typical structural elements development...