A5036174284- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Immune Response and Inflammation
- Ion channel regulation and function
- Immune cells in cancer
- Ion Channels and Receptors
- Sphingolipid Metabolism and Signaling
- Developmental Biology and Gene Regulation
- Inflammatory mediators and NSAID effects
- Inflammasome and immune disorders
- Neurogenesis and neuroplasticity mechanisms
- Hydrogen's biological and therapeutic effects
- Adenosine and Purinergic Signaling
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Eicosanoids and Hypertension Pharmacology
- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Lipid Membrane Structure and Behavior
- Chemokine receptors and signaling
- Connexins and lens biology
- Mangiferin and Mango Extracts
- Planarian Biology and Electrostimulation
- Cholesterol and Lipid Metabolism
- Glutathione Transferases and Polymorphisms
St George's, University of London
2009-2017
Institute of Infection and Immunity
2015
City St George's, University of London
2014
Universidad de Sevilla
2013
Paracelsus-Harz-Klinik Bad Suderode
2013
Ludwig-Maximilians-Universität München
2013
München Klinik Harlaching
2013
Martin Luther University Halle-Wittenberg
2013
Cellular Therapeutics (United Kingdom)
2013
CTI BioPharma (United Kingdom)
2013
Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1) and COX-2 enzymes. The NLRP3 inflammasome is a multi-protein complex responsible for the processing of proinflammatory cytokine interleukin-1β implicated in many inflammatory diseases. Here we show that several clinically approved widely used NSAIDs fenamate class are effective selective inhibitors via inhibition volume-regulated anion channel macrophages, independently COX Flufenamic acid mefenamic...
Abstract Migration of microglial cells towards damaged tissue plays a key role in central nervous system regeneration under pathological conditions. Using time lapse video microscopy we show that lysophosphatidic acid (LPA) enhances chemokinetic migration murine cells. In the presence 1 µ m LPA, mean rate was increased 3.8‐fold. patch‐clamp studies demonstrate LPA induces activation Ca 2+ ‐activated K + current. Microglial currents were abolished by either 50 n charybdotoxin or 10...
Production of reactive oxygen species (ROS) by microglial cells and subsequent oxidative stress are strongly implicated in the pathogenesis Alzheimer's disease. Although it is recognized that amyloid-β (Aβ) plays a major role inducing regulating ROS production disease, to date little known about cellular mechanisms underlying Aβ-stimulated production. Here, we identified ion channels involved Aβ-induced priming. Acute stimulation with either fibrillar Aβ1–42 (fAβ1–42) or soluble (sAβ1–42)...
NLRP3 is a receptor important for host responses to infection, yet also known contribute devastating diseases such as Alzheimer's disease, diabetes, atherosclerosis, and others, making inhibitors sought after. One of the currently in use 2-aminoethoxy diphenylborinate (2APB). Unfortunately, addition inhibiting NLRP3, 2APB displays non-selective effects on cellular Ca2+ homeostasis. Here, we chemical scaffold build series inhibitors, NBC series, which inhibit inflammasome vitro vivo without...
Ion channels play pivotal roles in regulating important functions of macrophages, such as cytokine and chemokine production, migration, proliferation, phagocytosis others. In this study, we have identified a novel ion channel type namely transient receptor potential M7 (TRPM7) channels. TRPM7 activity is differentially regulated i.e. current density significantly larger anti-inflammatory M2-type macrophages than untreated pro-inflammatory M1-type while mRNA levels remain unchanged upon cell...
The K + channel expression pattern of microglia strongly depends on the cells' microenvironment and has been recognized as a sensitive marker functional state. While numerous studies have performed in vitro , our knowledge about microglial channels their regulation vivo is limited. Here, we investigated currents striatum, neocortex entorhinal cortex young adult aged mice. Although almost all cells exhibited inward rectifier upon membrane hyperpolarization, mean current density was...
Abstract Differentiation of microglial cells is characterized by transformation from ameboid into ramified cell shape and up‐regulation K + channels. The processes differentiation are controlled astrocytic factors. mechanisms which astrocytes cause developmental changes in morphological electrophysiological properties microglia have remained unclear. We show here that the cytokines transforming growth factor‐β (TGF‐β), macrophage colony‐stimulating factor (M‐CSF) granulocyte/macrophage...
Abstract IL-1β released from activated macrophages contributes significantly to tissue damage in inflammatory, degenerative, and autoimmune diseases. In the present study, we identified a novel mechanism of release microglia (brain macrophages) that occurred independently P2X7 ATP receptor activation. Stimulation LPS-preactivated with lysophosphatidylcholine (LPC) caused rapid processing secretion mature 17-kDa IL-1β. Neither LPC-induced nor LPC-stimulated intracellular Ca2+ increases were...
Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage are hallmarks of brain aging, traumatic injury neurodegenerative diseases. It is, thus, particular interest identify mechanisms involved in microglial priming. Here, we demonstrate that microglia with interferon-γ (IFN γ) substantially production reactive oxygen species (ROS) following stimulation ATP. Priming ROS was reduced by inhibition p38 MAPK activity SB203580, increases intracellular...
Brain tissue damage following stroke or traumatic brain injury is accompanied by neuroinflammatory processes, while microglia play a central role in causing and regulating neuroinflammation via production of proinflammatory substances, including cytokines chemokines. Here, we used slices, an established situ model, from young adult aged mice to investigate cytokine chemokine with particular focus on the microglia. Twenty four hours after slice preparation, higher concentrations cytokines,...
Microglial activation is accompanied by changes in K + channel expression. Here we demonstrate that a deactivating cytokine the electrophysiological properties of microglial cells. Upregulation delayed rectifier (DR) channels was observed microglia after exposure to transforming growth factor-β (TGF-β) for 24 h. In contrast, inward expression unchanged TGF-β. DR current density more than sixfold larger TGF-β-treated untreated microglia. currents cells exhibited following properties: at...
Activation of microglial cells, the resident macrophages brain, occurs rapidly following brain injury. De-ramification, i.e. transformation from ramified into amoeboid morphology is one earliest manifestations activation. In present study, we identified physiological mechanisms underlying de-ramification induced by lysophosphatidylcholine (LPC). Patch-clamp experiments revealed activation non-selective cation currents and Ca(2+)-dependent K(+) extracellular LPC. LPC-activated channels were...
Voltage‐activated proton currents are reported for the first time in human peripheral blood T and B lymphocytes leukaemic cell line Jurkat E6‐1. The properties of H + studied using tight‐seal voltage‐clamp recording techniques were similar all cells. Changing pH gradient by one unit caused a 47 mV shift reversal potential, demonstrating high selectivity channels protons. current activation upon membrane depolarisation had sigmoidal course that could be fitted single exponential function...
Abstract Morphological, immunophenotypical and electrophysiological properties were investigated in isolated cultured murine microglia before after exposure to astrocyte‐conditioned medium (ACM). Following application of ACM, microglial cells underwent a dramatic shape transformation from an amoeboid appearance ramified morphology. In parallel morphological changes, downregulation macrophage surface antigens was observed exposed ACM. Staining intensities for major histocompatibility complex...
Abstract Lysophosphatidylcholine (LPC) is a major atherogenic lipid which stimulates the recruitment of monocytes to atherosclerotic lesions. The physiological mechanisms underlying LPC‐induced monocyte migration are poorly understood. Here we demonstrate that LPC activates non‐selective cation channels, significantly involved in chemotaxis monocytes. External elicited activation currents THP‐1 monocytes, occurred G protein and phospholipase C‐independent manner. LPC‐activated were almost...
Glycine is known to modulate immune cell responses. However, the physiological mechanisms underlying inhibitory effects of glycine on macrophages are not well understood. Here we show that capable inducing inward currents in brain (microglia). In contrast glycine, receptor agonist taurine failed elicit currents. Glycine-evoked were unaffected by strychnine, Cl(-)-free extracellular solution, N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl])sarcosine (NFPS) and amoxapine, but abolished upon...