A5090729869- Fatty Acid Research and Health
- Chronic Kidney Disease and Diabetes
- Eicosanoids and Hypertension Pharmacology
- Renal Diseases and Glomerulopathies
- Immune Response and Inflammation
- Renal and related cancers
- Adipokines, Inflammation, and Metabolic Diseases
- Connective Tissue Growth Factor Research
- Cholesterol and Lipid Metabolism
- Phagocytosis and Immune Regulation
- Cancer, Hypoxia, and Metabolism
- TGF-β signaling in diseases
- Immune cells in cancer
- Birth, Development, and Health
- S100 Proteins and Annexins
- Epigenetics and DNA Methylation
- Cell Adhesion Molecules Research
- Liver Disease Diagnosis and Treatment
- Protein Kinase Regulation and GTPase Signaling
- Atherosclerosis and Cardiovascular Diseases
- Inflammatory mediators and NSAID effects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Advanced Glycation End Products research
- Genetic Associations and Epidemiology
- Systemic Sclerosis and Related Diseases
University College Dublin
2015-2024
Mater Misericordiae University Hospital
1999-2021
Conway School of Landscape Design
2004-2017
Health Research Board
2017
Harvard University Press
2014
GTx (United States)
2011
Ospedale L. Bonomo
2007
Diabetes Research Center
2007
William Harvey Research Institute
2007
Molecular Medicine Ireland
2001-2006
A G protein-coupled receptor for the pineal hormone melatonin was recently cloned from mammals and designated Mel1a receptor. We now report cloning of a second humans designate it Mel1b The cDNA encodes protein 362 amino acids that is 60% identical at acid level to human Transient expression in COS-1 cells results high-affinity 2-[125I]iodomelatonin binding (Kd = 160 +/- 30 pM). In addition, rank order inhibition specific by eight ligands similar exhibited Functional studies NIH 3T3 stably...
Hypoxia is a feature of the microenvironment growing tumor. The transcription factor NFkappaB activated in hypoxia, an event that has significant implications for tumor progression. Here, we demonstrate hypoxia activates through pathway involving activation IkappaB kinase-beta (IKKbeta) leading to phosphorylation-dependent degradation IkappaBalpha and liberation NFkappaB. Furthermore, increasing pool and/or potential IKKbeta, amplifies cellular sensitivity stimulation with TNFalpha. Within...
Abstract Lipoxins (LX) are lipoxygenase-derived eicosanoids generated during inflammation. LX inhibit polymorphonuclear neutrophil (PMN) chemotaxis and adhesion putative braking signals for PMN-mediated tissue injury. In this study, we report that LXA4 promotes another important step in the resolution phase of inflammation, namely, phagocytosis apoptotic PMN by monocyte-derived macrophages (Mφ). triggered rapid, concentration-dependent uptake PMN. This bioactivity was shared stable synthetic...
Accumulation of mesangial matrix is a pivotal event in the pathophysiology diabetic nephropathy. The molecular triggers for production are still being defined. Here, suppression subtractive hybridization identified 15 genes differentially induced when primary human cells exposed to high glucose (30 mm versus 5 mm) vitro. These included (a) known regulators cell activation nephropathy (fibronectin, caldesmon, thrombospondin, and plasminogen activator inhibitor-1), (b) novel genes, (c) whose...
The advancement of microRNA (miRNA) therapies has been hampered by difficulties in delivering miRNA to the injured kidney a robust and sustainable manner. Using bioluminescence imaging mice with unilateral ureteral obstruction (UUO), we report that mesenchymal stem cells (MSCs), engineered overexpress miRNA-let7c (miR-let7c-MSCs), selectively homed damaged kidneys upregulated miR-let7c gene expression, compared nontargeting control (NTC)-MSCs. miR-let7c-MSC therapy attenuated injury...
Significance Statement Although studies show that diabetic kidney disease has a heritable component, searches for the genetic determinants of this complication diabetes have had limited success. In study, new international genomics consortium, JDRF funded Diabetic Nephropathy Collaborative Research Initiative, assembled nearly 20,000 samples from participants with type 1 diabetes, and without disease. The authors found 16 disease–associated loci at genome-wide significance. strongest signal...
Abstract The resolution of inflammation is a dynamically regulated process that may be subverted in many pathological conditions. Macrophage (Mφ) phagocytic clearance apoptotic leukocytes plays an important role the as this prevents exposure tissues at inflammatory site to noxious contents lytic cells. It increasingly appreciated endogenously produced mediators, such lipoxins, act potent regulators (nanomolar range) In study, we have investigated intriguing possibility cells release signals...
ABSTRACT. Lipoxins (LX) are eicosanoids with antiinflammatory activity in glomerulonephritis (GN) and inflammatory diseases, hypersensitivity, ischemia reperfusion injury. It has been demonstrated that LXA<sub>4</sub> stimulates non-phlogistic phagocytosis of apoptotic polymorphonuclear neutrophils (PMN) by monocyte-derived macrophages (Mφ) <i>in vitro</i>, suggesting a role for LX as endogenous pro-resolution lipid mediators. is here reported LXA<sub>4</sub>, LXB<sub>4</sub>, the...
The recent cloning of a family high affinity melatonin receptors has provided us with unique opportunity to define the signal transduction pathways used by these receptors. We have studied signaling through human Mel1a receptor subtype stable expression complementary DNA in NIH 3T3 cells. Our data indicate that is coupled inhibition forskolin-stimulated cAMP accumulation pertussis toxin-sensitive G protein. Although alone without effect on phosphoinositide hydrolysis, it potentiates effects...
Abstract Phagocytic clearance of apoptotic leukocytes plays an important role in the resolution inflammation. The glucocorticoid-inducible protein annexin 1 and 1-derived peptides show potent anti-inflammatory responses acute chronic In this study, we report that peptide (Ac2–26) significantly stimulates nonphlogistic phagocytosis polymorphonuclear (PMNs) by human monocyte-derived macrophages (Mφ). Peptide Ac2–26-stimulated is accompanied rearrangement Mφ actin cytoskeleton. To investigate...
REVIEW article Front. Immunol., 10 October 2011Sec. Inflammation volume 2 - 2011 | https://doi.org/10.3389/fimmu.2011.00052
Lipoxins (LXs) are endogenously produced eicosanoids with well-described anti-inflammatory and proresolution activities, stimulating nonphlogistic phagocytosis of apoptotic cells by macrophages. LXA4 the glucocorticoid-derived annexin A1 peptide (Ac2–26) bind to a common G-proteincoupled receptor, termed FPR2/ALX. However, direct evidence involvement FPR2/ALX in activity is still be investigated. Here we describe trafficking response Ac2–26 stimulation. We have transfected HA-tagged studied...
The let-7 miRNA family plays a key role in modulating inflammatory responses. Vascular smooth muscle cell (SMC) proliferation and endothelial (EC) dysfunction are critical the pathogenesis of atherosclerosis, including setting diabetes. Here we report that levels decreased diabetic human carotid plaques model diabetes-associated ApoE-/- mouse. In vitro platelet-derived growth factor (PDGF)- tumor necrosis factor-α (TNF-α)-induced vascular SMC EC activation was associated with reduced...
Lipoxins, which are endogenously produced lipid mediators, promote the resolution of inflammation, and may inhibit fibrosis, suggesting a possible role in modulating renal disease. Here, lipoxin A4 (LXA4) attenuated TGF-β1–induced expression fibronectin, N-cadherin, thrombospondin, notch ligand jagged-1 cultured human proximal tubular epithelial (HK-2) cells through mechanism involving upregulation microRNA let-7c. Conversely, TGF-β1 suppressed In pretreated with LXA4, let-7c persisted...
Unresolved inflammation underlies the development of fibrosis and organ failure. Here, we investigate potential proresolving eicosanoid lipoxinA4 (LXA4) its synthetic analog benzo-LXA4 to prophylactically modulate fibrotic inflammatory responses in a model early renal fibrosis, unilateral ureteric obstruction (UUO). Male Wistar rats (Animalia, Chordata, Rattus norvegicus) were injected intravenously with vehicle (0.1% ethanol), LXA4 (45 μg/250-g rat), or (15 rat) 15 min prior surgery...