A5015671418- Cell death mechanisms and regulation
- NF-κB Signaling Pathways
- interferon and immune responses
- Immune Response and Inflammation
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Ubiquitin and proteasome pathways
- Neonatal Respiratory Health Research
- Autophagy in Disease and Therapy
- Phagocytosis and Immune Regulation
- Inflammasome and immune disorders
- Mycobacterium research and diagnosis
- Oral microbiology and periodontitis research
- Viral Infections and Outbreaks Research
- Erythrocyte Function and Pathophysiology
- Endoplasmic Reticulum Stress and Disease
- Respiratory Support and Mechanisms
- Sinusitis and nasal conditions
- RNA Interference and Gene Delivery
- Mitochondrial Function and Pathology
- Lipoproteins and Cardiovascular Health
- PARP inhibition in cancer therapy
- Helicobacter pylori-related gastroenterology studies
- Trace Elements in Health
- Gut microbiota and health
- SARS-CoV-2 and COVID-19 Research
VIB-UGent Center for Inflammation Research
2014-2022
Ghent University
2012-2022
Vlaams Instituut voor Biotechnologie
2022
Joint Research Center
2016-2017
Although mixed lineage kinase domain-like (MLKL) protein has emerged as a specific and crucial for necroptosis induction, how MLKL transduces the death signal remains poorly understood. Here, we demonstrate that full four-helical bundle domain (4HBD) in N-terminal region of is required sufficient to induce its oligomerization trigger cell death. Moreover, found patch positively charged amino acids on surface 4HBD binds phosphatidylinositol phosphates (PIPs) allows recruitment plasma...
Abstract RIPK1 regulates cell death and inflammation through kinase-dependent -independent mechanisms. As a scaffold, inhibits caspase-8-dependent apoptosis RIPK3/MLKL-dependent necroptosis. kinase, paradoxically induces these modalities. The molecular switch between pro-survival pro-death functions remains poorly understood. We identify phosphorylation of on Ser25 by IKKs as key mechanism directly inhibiting kinase activity preventing TNF-mediated RIPK1-dependent death. Mimicking (S > D...
Background Chronic airway inflammation is the main driver of pathogenesis in respiratory diseases such as severe asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF) and bronchiectasis. While role common pathogens widely recognised, influence other microbiota members still poorly understood. Methods We hypothesised that lung contains bacteria with immunomodulatory activity which modulate net levels immune activation by key pathogens. Therefore, we assessed effect several...
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...
Rationale: Respiratory syncytial virus (RSV) bronchiolitis causes significant infant mortality. Bronchiolitis is characterized by airway epithelial cell (AEC) death; however, the mode of death remains unknown.Objectives: To determine whether necroptosis contributes to RSV pathogenesis via HMGB1 (high mobility group box 1) release.Methods: Nasopharyngeal samples were collected from children presenting hospital with acute respiratory infection. Primary human AECs and neonatal mice inoculated...
Plasma membrane permeabilization (PMP) is a defining feature of regulated necrosis. It allows the extracellular release damage-associated molecular patterns (DAMPs) that trigger sterile inflammation. The pore forming molecules MLKL and GSDMs drive PMP in necroptosis pyroptosis, respectively, but process remains unclear many other forms Here, we identified NINJ1 as crucial regulator consequent DAMP during ferroptosis, parthanatos, H2O2-induced necrosis secondary Importantly,...
Background Receptor-interacting protein kinase 1 (RIPK1) is a key mediator of regulated cell death (including apoptosis and necroptosis) inflammation, both drivers COPD pathogenesis. We aimed to define the contribution RIPK1 kinase-dependent inflammation in pathogenesis COPD. Methods assessed expression single-cell RNA sequencing (RNA-seq) data from human mouse lungs, validated levels lung tissue patients via immunohistochemistry. Next, we consequences genetic pharmacological inhibition...
Receptor-interacting protein kinase 1 (RIPK1) is an important component of the tumor necrosis factor receptor (TNFR1) signaling pathway. Depending on cell type and conditions, RIPK1 mediates MAPK NF-κB activation as well death. Using a mutant form (RIPK1ΔID) lacking intermediate domain (ID), we confirm requirement this for these events. Moreover, expression RIPK1ΔID resulted in enhanced recruitment caspase-8 to TNFR1 complex II Fas-associated death (FADD), which allowed shift from...
Abstract Butylate hydroxyanisole (BHA) is a synthetic phenol that widely utilized as preservative by the food and cosmetic industries. The antioxidant properties of BHA are also frequently used scientists to claim implication reactive oxygen species (ROS) in various cellular processes, including cell death. We report on surprising finding functions direct inhibitor RIPK1, major signaling hub downstream several immune receptors. Our silico analysis predicts binding 3-BHA, but not 2-BHA, RIPK1...
Abstract The sensitivity of cells to death receptor-induced apoptosis is commonly controlled by multiple checkpoints in order limit induction excessive or unnecessary death. Although cytotoxic various cancer cells, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) does not trigger most non-transformed cells. molecular nature the that normally protect from TRAIL-induced are fully understood. Endoplasmic reticulum (ER) stress has been reported switch human effect TRAIL,...
The Inhibitor of Kappa B Kinase (IKK) complex is a critical regulator NF-κB activation. More recently, IKK has also been shown to repress RIPK1 dependent extrinsic cell death pathways by directly phosphorylating at serine 25. In T cells, expression essential for normal development in the thymus, promoting survival thymocytes independently undergoes extensive phosphorylation following TNF stimulation though which targets are required not defined. Here, we show that induced S25 dependent. We...
RIPK1 (receptor-interacting serine/threonine-protein kinase 1) enzymatic activity drives both apoptosis and necroptosis, a regulated form of necrosis. Because necroptosis is involved in necrotic core development atherosclerotic plaques, we investigated the effects RIPK1S25D/S25D mutation, which prevents activation kinase, on atherogenesis ApoE−/− mice. After 16 weeks western-type diet (WD), plaques from mice were significantly larger compared to RIPK1+/+ (167 ± 34 vs. 78 18 × 103 µm2, p =...
Chronic Obstructive Pulmonary Disease (COPD) is characterized by chronic inflammation of the lungs and exaggerated cell death, leading to emphysema airway remodeling. We hypothesize that cigarette smoke (CS), main risk factor for COPD, activates Receptor Interacting Protein Kinase-1 (RIPK1), a key regulator death. investigated RIPK1 levels in patients with without COPD assessed consequences genetic pharmacological inhibition kinase function short long-term mouse models. RIPK1 protein...