A5009694951- Inflammasome and immune disorders
- Hair Growth and Disorders
- Bone Metabolism and Diseases
- Heme Oxygenase-1 and Carbon Monoxide
- Geochemistry and Geologic Mapping
- Autoimmune and Inflammatory Disorders Research
- Geological and Geochemical Analysis
- Neuroscience and Neuropharmacology Research
- Sphingolipid Metabolism and Signaling
- Autoimmune Bullous Skin Diseases
- Skin and Cellular Biology Research
- Immune Response and Inflammation
- Bone health and osteoporosis research
- interferon and immune responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Planetary Science and Exploration
- Dermatologic Treatments and Research
- Natural product bioactivities and synthesis
- Photosynthetic Processes and Mechanisms
- High-pressure geophysics and materials
- Atherosclerosis and Cardiovascular Diseases
- T-cell and B-cell Immunology
- Bone health and treatments
- Gout, Hyperuricemia, Uric Acid
- Neonatal Health and Biochemistry
University of Manchester
2018-2024
Manchester Academic Health Science Centre
2018-2024
St Vincent's Hospital
2000-2024
St. Anthony’s Hospital
2024
Skin Health Institute
2023
The University of Melbourne
2000-2023
Institut de Biologie du Développement Marseille
2020
Aix-Marseille Université
2020
Centre National de la Recherche Scientifique
2020
Institute of Immunology
2020
The NLRP3 inflammasome is an important regulator of inflammation and immunity. It a multimolecular platform formed within cells that facilitates the activation proinflammatory caspases to drive secretion cytokines such as interleukin-1β (IL-1β). Knowledge mechanisms regulating formation incomplete. Here we report Cl- channel-dependent dynamic ASC oligomers specks remain inactive in absence K+ efflux. Formed after efflux exclusively, are dependent, reversible, inactive, although they further...
ABSTRACT The Runt related transcription factors RUNX (AML/CBFα/PEBP2α) are key regulators of hematopoiesis and osteogenesis. Using co-transfection experiments with four natural promoters, including those the osteocalcin (OC), multi drug resistance (MDR), Rous Sarcoma Virus long terminal repeat (LTR), bone sialoprotein (BSP) genes, we show that each these promoters responds differently to forced expression proteins. However, three subtypes (i.e. AML1, AML2, AML3) regulate promoter in a...
Abstract Cbfa1/Runx2 is a transcription factor essential for bone formation and osteoblast differentiation. Two major N-terminal isoforms of Cbfa1, designated type I/p56 (PEBP2aA1, starting with the sequence MRIPV) II/p57 (til-1, MASNS), each regulated by distinct promoters, are known. Here, we show that I transcript constitutively expressed in nonosseous mesenchymal tissues progenitor cells. Cbfa1 isoform expression does not change differentiation status In contrast, II increased during...
Article11 September 2018Open Access Source DataTransparent process USP7 and USP47 deubiquitinases regulate NLRP3 inflammasome activation Pablo Palazón-Riquelme Division of Infection, Immunity Respiratory Medicine, Faculty Biology, Medicine Health, Manchester Collaborative Centre Inflammation Research, Academic Health Science Centre, Core Technology Facility, School Biological Sciences, University Manchester, UK Search for more papers by this author Jonathan D Worboys Jack Green Neuroscience...
Abstract Alopecia areata ( AA ) severity varies from a single small patch to complete loss of scalp hair, body eyelashes and eyebrows. While 40% all affected individuals only ever get one will achieve spontaneous durable remission within 6 months, 27% develop additional patches but still 12 months 33% chronic . Without systemic treatment, 55% with have persistent multifocal relapsing remitting disease, 30% ultimately alopecia totalis 15% universalis. The unpredictable course psychological...
Research Article| September 01, 1959 GEOCHEMICAL TABLE OF THE ELEMENTS FOR JACK GREEN AERO-SPACE LABORATORIES, NORTH AMERICAN AVIATION, MISSILE DIVISION, DOWNEY, CALIFORNIA Search for other works by this author on: GSW Google Scholar Author and Article Information Publisher: Geological Society of America Received: 02 Jul 1958 First Online: Mar 2017 Online ISSN: 1943-2674 Print 0016-7606 Copyright © 1959, The America, Inc. is not claimed on any material prepared U.S. government employees...
Alzheimer's disease is a devastating neurodegenerative with dramatically increasing prevalence and no disease-modifying treatment. Inflammatory lifestyle factors increase the risk of developing disease. Zinc deficiency most prevalent malnutrition in world may be factor for potentially through enhanced inflammation, although evidence this limited. Here we provide epidemiological suggesting that zinc supplementation was associated reduced slower cognitive decline, people mild impairment. Using...
Abstract The NLRP3 inflammasome is a multiprotein complex that regulates caspase‐1 activation and subsequent interleukin (IL)‐1β IL‐18 release from innate immune cells in response to infection or injury. Derivatives of the metabolites itaconate fumarate, dimethyl (DMI), 4‐octyl (4OI) fumarate (DMF) limit both expression IL‐1β following activation. However, direct effects these metabolite derivatives on responses require further investigation. Using murine bone marrow‐derived macrophages,...
Inflammation driven by the NLRP3 inflammasome is coordinated through multiple signaling pathways and regulated subcellular organelles. Here, we tested hypothesis that senses disrupted endosome trafficking to trigger formation inflammatory cytokine secretion. NLRP3-activating stimuli triggered localization of vesicles positive for endolysosomal markers inositol lipid PI4P. Chemical disruption sensitized macrophages activator imiquimod, driving enhanced activation Together, these data suggest...
The risk of early recurrent events after stroke remains high despite currently established secondary prevention strategies1. Risk is particularly in patients with atherosclerosis, more than 10% experiencing events1,2. However, the enormous medical burden this clinical phenomenon, underlying mechanisms leading to increased vascular and are largely unknown. Here, using a novel mouse model stroke-induced ischaemia, we show that leads activation AIM2 inflammasome vulnerable atherosclerotic...
Excessive or aberrant NLRP3 inflammasome activation has been implicated in the progression and initiation of many inflammatory conditions; however, currently no inhibitors have approved for therapeutic use clinic. Here we identified that natural product brazilin effectively inhibits both priming cultured murine macrophages, a human iPSC microglial cell line mouse model acute peritoneal inflammation. Through computational modeling, predict can adopt favorable binding pose within site protein...
The runt family transcription factor (AML-3/PEBP2αA1/Cbfa1/RUNX2) plays a crucial role in formation of the mineralized skeleton during embryogenesis and regulates maturation osteoblast phenotype. Because steroid hormones growth factors significantly influence differentiation properties osteoblasts, we addressed Cbfa1 as target gene for regulation by dexamethasone (Dex), 1,25(OH)D3 (vitamin D3), 17β-estradiol, transforming factor-β1 (TGF-β1). representation functional protein levels Western...
Abstract Mechanisms controlling human bone formation remain to be fully elucidated. We have used differential display‐polymerase chain reaction analysis characterize osteogenic pathways in conditionally immortalized osteoblasts (HOBs) representing distinct stages of differentiation. identified 82 differentially expressed messages and found that the Wnt antagonist secreted frizzled‐related protein (sFRP)‐1 was most highly regulated these. Transient transfection HOBs with sFRP‐1 suppressed...
The mouse MC3T3-E1 cell line is nontumorigenic and undergoes a typical program of osteoblast differentiation in vitro, producing bone-like mineralized extracellular matrix. We report responses these cells to dexamethasone (Dex) 1,25-(OH)2D3 that are contrast findings from other culture systems. First, chronic exposure both early- late-passaged 10−7m Dex, initiated during the proliferation period, blocked differentiation, enhanced observed cultures fetal rat calvarial-derived cells. Secondly,...
Interleukin (IL)-1 family cytokines potently regulate inflammation, with the majority of IL-1 proteins being secreted from immune cells via unconventional pathways. In many cases, secretion appears to be closely coupled cell death, yet secretory mechanisms involved remain poorly understood. Here, we studied three best-characterized members superfamily, IL-1α, IL-1β, and IL-18, in a range conditions types, including murine bone marrow–derived peritoneal macrophages, human monocyte–derived...
Summary Excessive and dysregulated inflammation is known to contribute disease progression. HSP90 an intracellular chaperone regulate inflammatory processes including the NLRP3 inflammasome secretion of pro‐inflammatory cytokine interleukin(IL)‐1β. Here, primarily using in vitro ASC speck assay, vivo model murine peritonitis, we tested utility inhibitors as anti‐inflammatory molecules. We report that inhibitor EC144 effectively inhibited priming activation . A specific β isoform was...
Inflammation driven by DNA sensors is now understood to be important disease pathogenesis. Here, we describe new inhibitors of sensing, primarily the inflammasome forming sensor AIM2. Biochemistry and molecular modeling has revealed 4-sulfonic calixarenes as potent AIM2 that likely work binding competitively DNA-binding HIN domain. Although less potent, these also inhibit cGAS TLR9 demonstrating a broad utility against DNA-driven inflammatory responses. The inhibited AIM2-dependent...
Current measures of alopecia areata (AA) severity, such as the Severity Alopecia Tool score, do not adequately capture overall disease impact.
Estrogen responsiveness of bone is a fundamental regulatory mechanism operative in skeletal homeostasis. We examined the expression estrogen receptor-α (ER) messenger RNA (mRNA) cultured rat calvarial-derived osteoblasts during progressive development osteoblast phenotype. Levels ER message were compared with traditional osteoblastic markers that have been mapped throughout differentiation process these cells. transcripts, measured using semiquantitative RT-PCR analysis, expressed at low...
Histone deacetylase (HDAC) inhibitors have shown promise in treating various forms of cancer. However, many HDAC from diverse structural classes been associated with QT prolongation humans. Inhibition the human ether a-go-go related gene (hERG) channel has and fatal arrhythmias. To determine if observed cardiac effects humans is due to hERG blockade, a highly potent inhibitor devoid activity was required. Starting dacinostat (LAQ824), inhibitor, we explored SAR pharmacophores required for...
The NLRP3 inflammasome is a multi-molecular protein complex that converts inactive cytokine precursors into active forms of IL-1β and IL-18. frequently associated with the damaging inflammation non-communicable disease states considered an attractive therapeutic target. However, there much regarding mechanism activation remains unknown. Chloride efflux suggested as important step in activation, but which chloride channels are involved still We used chemical, biochemical, genetic approaches...
SUMMARY Misconceptions exist in the community regarding factors that exacerbate acne vulgaris. In particular stress, diet, lifestyle and personal hygiene are often erroneously claimed to be important factors. order investigate whether these common misconceptions persist medical graduates, we analysed answers of 215 sixth year students, who all subsequently graduated from The University Melbourne, a short‐answer question on management exacerbating one their final examination papers. With...