A5028521025- Blood Coagulation and Thrombosis Mechanisms
- Osteoarthritis Treatment and Mechanisms
- Protease and Inhibitor Mechanisms
- Rheumatoid Arthritis Research and Therapies
- Cell Adhesion Molecules Research
- Knee injuries and reconstruction techniques
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Receptor Mechanisms and Signaling
- Extracellular vesicles in disease
- Inflammatory mediators and NSAID effects
- Renal function and acid-base balance
- Total Knee Arthroplasty Outcomes
- Nitric Oxide and Endothelin Effects
- Pain Mechanisms and Treatments
- Neonatal Respiratory Health Research
- Cytokine Signaling Pathways and Interactions
- Asthma and respiratory diseases
- Autoimmune and Inflammatory Disorders Research
- Systemic Lupus Erythematosus Research
- Bone fractures and treatments
- Neuropeptides and Animal Physiology
- Eicosanoids and Hypertension Pharmacology
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Connective tissue disorders research
- MicroRNA in disease regulation
University of the West of Scotland
2013-2024
Health & Life (Taiwan)
2024
Hamilton Medical (Switzerland)
2024
NHS Lanarkshire
2024
University of Glasgow
1996-2018
University of Strathclyde
2005-2014
University of Liverpool
2014
Newcastle University
2014
University of Nottingham
2012
University of Bristol
2012
Using physiological, pharmacological, and gene disruption approaches, we demonstrate that proteinase-activated receptor-2 (PAR-2) plays a pivotal role in mediating chronic inflammation. an adjuvant monoarthritis model of inflammation, joint swelling was substantially inhibited PAR-2–deficient mice, being reduced by more than fourfold compared with wild-type virtually no histological evidence damage. Mice heterozygous for PAR-2 showed intermediate phenotype. expression, normally limited to...
Using physiological, pharmacological, and gene disruption approaches, we demonstrate that proteinase-activated receptor-2 (PAR-2) plays a pivotal role in mediating chronic inflammation. an adjuvant monoarthritis model of inflammation, joint swelling was substantially inhibited PAR-2–deficient mice, being reduced by more than fourfold compared with wild-type virtually no histological evidence damage. Mice heterozygous for PAR-2 showed intermediate phenotype. expression, normally limited to...
Biological therapies such as tumor necrosis factor-α inhibitors have advanced the treatment of rheumatoid arthritis, but one-third patients do not respond to therapy. Furthermore, these are now usually administered in combination with conventional disease-modifying antirheumatic drugs, suggesting they achieved their early promise. This study investigates a novel therapeutic target, proteinase-activated receptor (PAR)-2, joint inflammation. Intra-articular carrageenan/kaolin (C/K) injection...
Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone changes OA order to further elucidate the role PAR2 pathogenesis. was induced wild-type (WT) PAR2-deficient (PAR2-/-) mice by destabilisation medial meniscus (DMM). Inflammation, were monitored using histology...
Abstract Objective Serine proteinases activate the G protein–coupled receptor, proteinase‐activated receptor 2 (PAR‐2), via cleavage and exposure of a tethered ligand. PAR‐2 is known to exert proinflammatory actions in murine model arthritis, since PAR‐2–deficient mice exhibit strikingly reduced articular inflammation. This study was undertaken examine synovial expression determine effect novel antagonist on cytokine production, order investigate hypothesis that plays critical role...
Increasing evidence implicates serine proteinases in pathologic tissue turnover. The aim of this study was to assess the role transmembrane proteinase matriptase cartilage destruction osteoarthritis (OA).Serine gene expression femoral head obtained from either patients with hip OA or fracture neck femur (NOF) assessed using a low-density array. effect on collagen breakdown determined degradation models, while matrix metalloproteinase (MMP) analyzed by real-time polymerase chain reaction....
Abstract Objective Angiotensin II (Ang II) is known to have proinflammatory actions, and Ang type 1 (AT ) receptors are up‐regulated in the rheumatoid synovium, suggesting that this receptor could be a therapeutic target. The purpose of study was investigate antiinflammatory potential selective AT antagonist losartan, which currently used for treatment cardiovascular disease. Methods Dose‐ranging studies losartan (1–50 mg/kg) were initially conducted rat model acute (carrageenan/kaolin)...
Iontophoretic assessment of skin microvascular function is complicated by the occurrence electrically induced hyperaemia, especially at cathode. Studies were performed to identify means reducing such effects. Skin vasodilator responses measured using a laser Doppler imager that controlled iontophoretic current delivery. A novel feature involved monitoring voltage across iontophoresis chambers. Comparison between vehicle (distilled H<sub>2</sub>O), acetylcholine (ACh) and sodium...
Mast cells are hypothesized to play a role in the pathogenesis of rheumatoid arthritis (RA) by mechanisms requiring elucidation. Tryptase released from these can activate protease-activated receptor 2 (PAR-2), which was recently shown have proinflammatory actions. The purpose this study examine relationship between synovial mast and PAR-2. cell proximity PAR-2-expressing investigated RA synovium. In murine studies, we assessed capacity tryptase mediate responses via PAR-2 whether...
Objective Osteoarthritis is a global clinical challenge for which no effective disease-modifying agents currently exist. This study identified protease-activated receptor 2 (PAR-2) as novel pathogenic mechanism and potential therapeutic target in osteoarthritis. Methods Experimental osteoarthritis was induced wild-type PAR-2-deficient mice by sectioning the medial meniscotibial ligament (MMTL), leading to development of mild arthropathy. Cartilage degradation increased subchondral bone...
Increasing evidence implicates serine proteinases in the proteolytic cascades leading to pathological destruction of extracellular matrices such as cartilage osteoarthritis (OA). We have previously demonstrated that type II transmembrane proteinase (TTSP) matriptase acts a novel initiator via induction and activation matrix metalloproteinases (MMPs). Hepsin is another TTSP expressed OA we hypothesized this may also contribute turnover. Herein, demonstrate addition hepsin explant culture...
<h3>Objective</h3> Proteinase-activated receptor-2 (PAR<sub>2</sub>) has been implicated in inflammatory articular pathology. Using the collagen-induced arthritis model (CIA) authors have explored capacity of PAR<sub>2</sub> to regulate adaptive immune pathways that could promote autoimmune mediated damage. <h3>Methods</h3> gene deletion and other approaches inhibit or prevent activation, development progression CIA were assessed via clinical histological scores together with ex vivo...
<h3>Objectives</h3> Proteinase-activated receptor 2 (PAR<sub>2</sub>) is a G protein-coupled activated by serine proteinases with proinflammatory activity. A study was undertaken to investigate the presence and functio©nal significance of PAR<sub>2</sub> expression on rheumatoid arthritis (RA)-derived leucocyte subsets. <h3>Methods</h3> Venous blood obtained from patients RA osteoarthritis (OA) as well healthy control subjects. Surface peripheral mononuclear cells (PBMCs) analysed flow...
Recent evidence indicates that microbial biofilm aggregates inhabit the lungs of COPD patients and actively contribute towards chronic colonization repeat infections. However, there are no contextually relevant complex models for research. In this study, a meta-analysis lung microbiome in was used to inform development an optimized model composed genera highly associated with COPD. Bioinformatic analysis showed although diversity matrices microbiomes were similar healthy controls, internal...
Proteinase-activated receptor-2 (PAR-2) was shown to influence immune regulation; however, its role in human macrophage subset development and function has not been addressed. Here, PAR-2 expression activation investigated on granulocyte (GM)-CSF(M1) (M)-CSF(M2) macrophages. In both macrophages, the PAR-2-activating peptide, SLIGKV, increased regulated TNF-α IL-10 secretion a manner similar LPS. addition, HLA-DR M1 cells also increased. Monocytes matured an phenotype presence of SLIGKV had...
Exercise is recommended as a non-pharmacological therapy for osteoarthritis (OA). Various exercise regimes, with differing intensities and duration, have been used in range of OA rodent models. These studies show gentle or moderate reduces the severity parameters while high intensity load bearing detrimental. However, these were largely conducted rats mouse models induced by severe injury, age obesity, whilst destabilization medial meniscus (DMM) mice has become widely accepted model due to...
An increase in medullary blood flow has been implicated as a mediator of the natriuresis following increases renal perfusion pressure (RPP). We examined whether administration L-arginine, substrate for nitric oxide production, restores impaired vasa recta hemodynamic response to RPP and blunted spontaneously hypertensive rat (SHR). The descending (QDVR) ascending (QAVR) urinary sodium excretion (UNaV) was increased by means an adjustable aortic clamp placed above arteries young SHR...