A5014899516- S100 Proteins and Annexins
- Neonatal Respiratory Health Research
- Fatty Acid Research and Health
- Immune Response and Inflammation
- Mosquito-borne diseases and control
- Viral Infections and Outbreaks Research
- Eicosanoids and Hypertension Pharmacology
- Diet and metabolism studies
- Neuropeptides and Animal Physiology
- Organ Transplantation Techniques and Outcomes
- Cancer-related gene regulation
- Intestinal and Peritoneal Adhesions
- Anesthesia and Neurotoxicity Research
- Immune Cell Function and Interaction
- Digestive system and related health
- Clinical Nutrition and Gastroenterology
- Inflammatory Bowel Disease
- Bone Metabolism and Diseases
- Medicinal Plant Pharmacodynamics Research
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Advanced Glycation End Products research
- Blood transfusion and management
- Ion Channels and Receptors
- Acute Kidney Injury Research
GlaxoSmithKline (United Kingdom)
2020-2025
Queen Mary University of London
2013-2022
William Harvey Research Institute
2013-2022
Age UK
2020-2021
Université Toulouse III - Paul Sabatier
2011-2014
Université de Toulouse
2011-2014
Centre de Physiopathologie de Toulouse-Purpan
2011-2014
Centre National de la Recherche Scientifique
2011-2014
Inserm
2011-2014
University of Parma
2008-2011
Bromodomain inhibitors revisited and extraterminal domain (BET) proteins contribute to the pathogenesis of cancer immune diseases through their effects on transcriptional regulation. BET contain two nearly identical bromodomains, BD1 BD2, structural modules that have attracted great interest as targets for drug development. First-generation drugs inhibited both BD2 showed promising therapeutic activity in preclinical models but proved be less efficacious clinical trials. Gilan et al. took a...
Significance Inflammation is a crucial host defense response but can cause chronic disease if unregulated. Several endogenous anti-inflammatory and proresolving circuits balance modulate inflammation, including mechanism centered on the formyl peptide receptor (FPR) family. One receptor, ALX/FPR2, recognizes both proinflammatory signals. We have investigated this unusual molecular finding that anti-inflammatory, not signals, activate homodimers of receptor. This triggers intracellular...
The resolution of inflammation is an active process orchestrated by specialized proresolving lipid mediators (SPM) that limit the host response within affected tissue; failure effective may lead to tissue injury. Because persistence inflammatory signals a main feature chronic conditions, including bowel diseases (IBDs), herein we investigate expression and functions SPM in intestinal inflammation. Targeted liquid chromatography-tandem mass spectrometry-based metabololipidomics was used...
Understanding the circuits that promote an efficient resolution of inflammation is crucial to deciphering molecular and cellular processes required tissue repair. Macrophages play a central role in regulation inflammation, resolution, repair/regeneration. Using model skeletal muscle injury repair, herein we identified annexin A1 (AnxA1) as extracellular trigger macrophage skewing toward pro-reparative phenotype. Brought into injured initially by migrated neutrophils, then overexpressed...
Significance Sepsis defines a syndrome with poor clinical management characterized by overlapping phases of excessive inflammation temporally aligned an immunosuppressed state. We define endogenous pathway centered on formyl-peptide receptor 2/3 (Fpr2/3)—ortholog to human FPR2/ALX (receptor for lipoxin A4)—that protects the host against polymicrobial sepsis. Using null mice and proof-of-concept experiments peptide–agonist, we demonstrate how engagement Fpr2/3 is crucial enact nonredundant...
Abstract Blood-derived monocytes remove apoptotic cells and terminate inflammation in settings as diverse atherosclerosis Alzheimer’s disease. They express high levels of the proresolving receptor ALX/FPR2, which is activated by protein annexin A1 (ANXA1), found abundance inflammatory exudates. Using primary human blood from healthy donors, we identified ANXA1 a potent CD14+CD16− monocyte chemoattractant, acting via ALX/FPR2. Downstream signaling pathway analysis revealed p38 MAPK-mediated...
Patients with CKD requiring dialysis have a higher risk of sepsis and 100-fold mortality rate than the general population sepsis. The severity cardiac dysfunction predicts in patients Here, we investigated effect preexisting on function mice whether inhibition I κ B kinase (IKK) reduces Male C57BL/6 underwent 5/6 nephrectomy, 8 weeks later, they were subjected to LPS (2 mg/kg) or by cecal ligation puncture (CLP). Compared sham operation, nephrectomy resulted significant increases urea...
Abstract There is a need for novel approaches to control pathologies with overexuberant inflammatory reactions. Targeting melanocortin (MC) receptors represents promising therapy obesity and chronic inflammation, but lack of selectivity safety concerns limit development. A new way increase biological effects entails the identification biased agonists. In this study, we characterize small molecule AP1189 as agonist at MC1 MC3. Although not provoking canonical cAMP generation, addition or MC3,...
Therapeutics promoting the endogenous production of IL-10 have potential to restore homeostasis in inflammatory disorders such as bowel disease (IBD). Here we describe identification a series upregulators based on pyrimidyl-piperidine scaffold through high throughput phenotypic CD4+ T-cell multiplex assay. In vitro optimization initial hit yielded lead with good potency and an clearance profile, compound 3–7, which additionally demonstrated efficacy murine endotoxin challenge PK–PD...
Living in a mentally and physically stimulating environment has been suggested to have beneficial effect on the immune response. This study investigates these effects, utilizing 2-week program of environmental enrichment (EE) 2 models acute inflammation: zymosan-induced peritonitis (ZIP) cecal ligation puncture (CLP) model sepsis. Our results revealed that following exposure EE, mice possessed significantly higher circulating neutrophil lymphocyte ratio compared with control animals. When...
Background and Purpose Hydrogen sulfide (H 2 S) is a gasotransmitter produced from l ‐cysteine through the enzymatic action of cystathionine‐γ‐lyase (CSE) and/or cystathionine‐β‐synthase. d ‐Penicillamine isomer dimethylated cysteine has been used for treatment rheumatoid arthritis. As ‐penicillamine structurally very similar to cysteine, we have investigated whether ‐penicillamine, as analogue, an effect on H S pathway. Experimental Approach We tested (0.01–1 mM) in mouse aortic rings...
Formyl peptide receptors (FPR) belong to a family of sensors the immune system that detect microbe-associated molecules and inform various cellular sensorial mechanisms presence pathogens in host. Here we demonstrate Fpr2/3-deficient mice show distinct profile behaviour characterised by reduced anxiety marble burying light-dark box paradigms, increased exploratory an open-field, together with superior performance on novel object recognition test. Pharmacological blockade formyl receptor...
Long-term intake of dietary fatty acids is known to predispose chronic inflammation, but their effects on acute intestinal ischaemia/reperfusion (I/R) injury unknown. The aim this study was determine the consequences a diet rich in n-3 or n-6 polyunsaturated (PUFA) I/R-induced damage.Mice were fed three different isocaloric diets: balanced used as control and two PUFA-enriched diets, providing either high levels PUFA. Intestinal evaluated after I/R. PUFA metabolites quantitated tissues by...
Host immune responses contribute to dengue’s pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known counterbalance overexuberant mast cell (MC) activation. We hypothesised inadequate AnxA1 engagement underlies cytokine storm vascular pathologies associated with dengue disease. Levels of were examined plasma patients infected mice....
Synthetic microstructures can be engineered to deliver bioactive compounds impacting on their pharmacokinetics and pharmacodynamics. Herein, we applied dextran-based layer-by-layer (LbL) microcapsules alpha-2-macroglobulin (α2MG), a protein with modulatory properties in inflammation. Extending recent observations made dextran-microcapsules loaded α2MG experimental sepsis, focused the physical chemical characteristics of these determined biology rodent human cells. We report an efficient...
Abstract Animal studies in pharmaceutical drug discovery are common preclinical research for compound evaluation before progression into human clinical trials. However, high rates of development attrition have prompted concerns regarding animal models and their predictive translatability to the clinic. To improve characterization translational relevance, authors developed a tool transparently reflect key features model that may be considered both application but also likelihood successful...
Polyunsaturated fatty acid (PUFA) metabolites are bioactive autoacoids that play an important role in the pathogenesis of a vast number pathologies, including gut diseases. The induction and resolution inflammation depend on PUFA metabolic pathways favored. Therefore, understanding profile n-6 (eicosanoids)/n-3 (docosanoids) PUFA-derived appear to be as gene or protein array approaches, uncover molecules potentially implicated inflammatory Using high sensitivity liquid chromatography tandem...
B-cell lymphoma 6 (BCL6) is a zinc finger transcriptional repressor possessing BTB–POZ (BR-C, ttk, and bab for BTB; pox virus POZ) domain, which required homodimerization association with corepressors. BCL6 has multiple roles in normal immunity, autoimmunity, some types of lymphoma. Mice bearing disrupted loci demonstrate suppressed high-affinity antibody responses to T-dependent antigens. The corepressor binding groove the domain potential target small compound-mediated therapy. Several...
Abstract Extensive morphological and neurochemical changes have been experimentally clinically documented in the hypertrophied intestine located orally to a chronic partial stenosis of lumen. Functional studies revealed not only disruption interdigestive motor complex vivo decreased efficiency contraction but also preservation peristaltic reflex vitro . Given critical role played intestinal peristalsis by coordinated activity longitudinal (LM) circular muscle (CM), this work focuses on...
Receptor-interacting protein 1 (RIP1) has emerged as a key for transducing signals induced by several immune receptors, including tumour necrosis factor receptor (TNFR 1).When these receptors are engaged, RIP1 kinase activity can drive cell death (apoptosis and necroptosis) proinflammatory cytokine production which been implicated in the pathogenesis of multiple inflammatory diseases 1,2 .To date, although driving inflammation tissues, data points to role intestines.Inflammatory bowel...