Research Topics
Genomes and Genes | Jane A MitchellSummaryAffiliation: Imperial College Country: UK Publications
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Publications
Cigarette smoke induces IL-8, but inhibits eotaxin and RANTES release from airway smooth muscleUte Oltmanns
Experimental Studies National Heart and Lung Institute, Imperial College, London SW36LY, UK
Respir Res 6:74. 2005..Human airway smooth muscle cells (HASMC) are a source of proinflammatory cytokines and chemokines. We investigated whether cigarette smoke could directly induce the release of chemokines from HASMC...
TOLLing away in BrazilJane A Mitchell
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
Nat Immunol 7:675-9. 2006- Critical role of toll-like receptors and nucleotide oligomerisation domain in the regulation of health and diseaseJane A Mitchell
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, Cardiac Medicine, Royal Brompton Hospital, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK
J Endocrinol 193:323-30. 2007..The role of pathogen-sensing pathways in disease is also discussed... - Role of pattern-recognition receptors in cardiovascular health and diseaseJ A Mitchell
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, Imperial College London, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, U K
Biochem Soc Trans 35:1449-52. 2007..We have identified examples of similarities and differences in how cardiovascular tissues and macrophages sense PAMPs. These findings will be discussed together with our interpretation of how this information may lead to new treatments... - Toll-like receptor 2 is essential for the sensing of oxidants during inflammationMark J Paul-Clark
Cardiothoracic Pharmacology, Cardiothoracic and Stem Cell Pharmacology, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, United Kingdom
Am J Respir Crit Care Med 179:299-306. 2009..The mechanisms by which oxidants are sensed by cells and cause inflammation are not well understood... - Differential regulation of CCL-11/eotaxin-1 and CXCL-8/IL-8 by gram-positive and gram-negative bacteria in human airway smooth muscle cellsRazao Issa
Experimental Studies, Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK
Respir Res 9:30. 2008..We hypothesize that bacteria and bacterial products could induce cytokine/chemokine release from ASMC... - Innate immunity in human embryonic stem cells: comparison with adult human endothelial cellsGabor Foldes
National Heart and Lung Institute, Imperial College, London, United Kingdom
PLoS ONE 5:e10501. 2010..TLR5 levels were similar between differentiated hESC and HAEC, and siRNA knockdown of TLR5 abolished the response to flagellin. These findings have potential implications for survival and function of grafted hESC-derived cells... - Gram-positive and Gram-negative bacteria synergize with oxidants to release CXCL8 from innate immune cellsMark J Paul-Clark
Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, United Kingdom
Mol Med 14:238-46. 2008..Thus an oxidant stimulation, possibly via an action on TLR2 or associated transduction pathways, provides a signal that initiates inflammatory responses and sensitizes cells to pathogenic insults... - Shape and compliance of endothelial cells after shear stress in vitro or from different aortic regions: scanning ion conductance microscopy studyClaire M F Potter
Cardiothoracic Pharmacology, Pharmacology and Toxicology and Functional Microscopy, Cardiovascular Sciences, National Heart and Lung Institute, London, United Kingdom
PLoS ONE 7:e31228. 2012.... 
PPARbeta/delta agonists modulate platelet function via a mechanism involving PPAR receptors and specific association/repression of PKCalpha--brief reportFerhana Y Ali
Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College London, London, UK
Arterioscler Thromb Vasc Biol 29:1871-3. 2009..As platelets are anucleated, the effects of PPARbeta/delta agonists on platelets must be nongenomic. Currently, the particular role of PPARbeta/delta receptors and their intracellular signaling pathways in platelets are not known...- Selective NOD1 agonists cause shock and organ injury/dysfunction in vivoNeil Cartwright
Department of Critical Care, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
Am J Respir Crit Care Med 175:595-603. 2007..In animal models, gram-negative septic shock is mimicked by lipopolysaccharide (LPS), which signals through Toll-like receptor 4 (TLR4) and its adaptor MyD88. The role of NLRs in the pathophysiology of septic shock is not known... - COX-1, and not COX-2 activity, regulates airway function: relevance to aspirin-sensitive asthmaLouise S Harrington
Cardiac Medicine, NHLI, Imperial College, Dovehouse St, London SW3 6LY, UK
FASEB J 22:4005-10. 2008..These observations show that despite the presence of COX-2, COX-1 is functionally predominant in the airways and explains clinical observations relating to drug specificity in patients with aspirin-sensitive asthma... - Reduced endothelial dependent vasodilation in vessels from TLR4(-/-) mice is associated with increased superoxide generationLouise S Harrington
Cardiothoracic Pharmacology, NHLI, Imperial College, Dovehouse Street, London, UK
Biochem Biophys Res Commun 408:511-5. 2011..These data implicate a novel cardio-protective role for TLR4 in vascular homeostasis... - Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular systemNicholas S Kirkby
Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom
Proc Natl Acad Sci U S A 109:17597-602. 2012.... - Role of RhoB in the regulation of pulmonary endothelial and smooth muscle cell responses to hypoxiaBeata Wojciak-Stothard
Centre for Pharmacology and Therapeutics, Experimental Medicine, Imperial College London, London, UK
Circ Res 110:1423-34. 2012..RhoB, a protein homologous to RhoA and activated by hypoxia, regulates neoplastic growth and vasoconstriction but its role in the regulation of pulmonary vascular function is not known... - Role of TLR2, TLR4, and MyD88 in murine ozone-induced airway hyperresponsiveness and neutrophiliaAlison S Williams
Experimental Studies Section, National Heart and Lung Institute, Imperial College London, Dovehouse St, London SW3 6LY, United Kingdom
J Appl Physiol 103:1189-95. 2007..Therefore, ozone may induce murine AHR and neutrophilic inflammation through the activation of the Toll-like receptor pathway that may sense noninfectious stimuli such as oxidative stress... - Inflammatory transcriptome profiling of human monocytes exposed acutely to cigarette smokeWilliam R Wright
Department of Cardiothoracic Pharmacology, Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, London, United Kingdom
PLoS ONE 7:e30120. 2012..The specific cellular mechanisms driving cigarette smoke-induced inflammation and disease are not fully understood, although the innate immune system is involved in the pathology of smoking related diseases... - Identification and characterization of a dysfunctional cardiac myocyte phenotype: role of bacteria, Toll-like receptors, and endothelinTrupti A Patel
Department of Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College London, London, United Kingdom
Shock 28:434-40. 2007..Description of the myocyte population, instead of effects only on individual cells, will be more relevant to the prediction of the depression of cardiac function... - Elucidation of toll-like receptor and adapter protein signaling in vascular dysfunction induced by gram-positive Staphylococcus aureus or gram-negative Escherichia coliNeil Cartwright
Department of Critical Care, National Heart and Lung Institute, Imperial College, London, UK
Shock 27:40-7. 2007..Our data are the first to establish the definitive roles of specific TLRs in the sensing of Gram-positive and Gram-negative bacteria by vessels and demonstrate that macrophages and blood vessels may differ in their response to pathogens... - Role of nitric oxide and prostacyclin as vasoactive hormones released by the endotheliumJane A Mitchell
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
Exp Physiol 93:141-7. 2008..The relative contribution of constitutive forms of NOS and COX, as well as interactions between IP, PPAR beta and guanylyl cyclase pathways in vessels and platelets, is discussed... - Role of Toll-like receptors 2 and 4 in the induction of cyclooxygenase-2 in vascular smooth muscleRosario Jimenez
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, Royal Brompton Hospital, Faculty of Medicine, Imperial College, London SW3 6LY, UK
Proc Natl Acad Sci U S A 102:4637-42. 2005..These data have important implications for our understanding of the innate immune response in vascular cells and how it may impact vascular disease... - Viral Toll Like Receptor activation of pulmonary vascular smooth muscle cells results in endothelin-1 generation; relevance to pathogenesis of pulmonary arterial hypertensionPeter M George
Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, United Kingdom
Biochem Biophys Res Commun 426:486-91. 2012..This may have importance in understanding the association between viruses and the development of PAH... - Differential effects of Gram-positive versus Gram-negative bacteria on NOSII and TNFalpha in macrophages: role of TLRs in synergy between the twoMark J Paul-Clark
1Cardiothoracic Pharmacology, Unit of Critical Care Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY
Br J Pharmacol 148:1067-75. 2006..6. These observations are the first to clearly delineate the role of separately activating TLR2 and TLR4 in the induction of NOSII and TNFalpha genes compared with their coinduction when both receptor pathways are activated... - Synergistic induction of endothelin-1 by tumor necrosis factor alpha and interferon gamma is due to enhanced NF-kappaB binding and histone acetylation at specific kappaB sitesStephen J Wort
Department of Critical Care, National Heart and Lung Institute, Imperial College London, London SW3 6LY, United Kingdom
J Biol Chem 284:24297-305. 2009..Understanding such mechanisms is crucial in determining the key control points in ET-1 release. This has particular relevance to developing novel treatments targeted at the inflammatory component of pulmonary vascular remodeling... - Antiplatelet actions of statins and fibrates are mediated by PPARsFerhana Y Ali
Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College, London, UK
Arterioscler Thromb Vasc Biol 29:706-11. 2009..These drugs inhibit platelet function, but the mechanisms by which this pleiotropic effect is exerted are not known... - Homeostatic role of Toll-like receptor 4 in the endothelium and heartLouise S Harrington
Cardiac, Vascular, and Inflammation Research, William Harvey Institute, Queen Mary s University of London, Charterhouse Square, London, EC1M 6BQ
J Cardiovasc Pharmacol Ther 12:322-6. 2007..These observations illustrate a novel role for TLR4 in the homeostatic control of a functional endothelium and, thereby, cardiovascular health... - The safety and side effects of monoclonal antibodiesTrevor T Hansel
Imperial Clinical Respiratory Research Unit, St Mary s Hospital, Paddington, London, UK
Nat Rev Drug Discov 9:325-38. 2010..Here, we review some of the adverse effects encountered with mAb therapies, and discuss advances in preclinical testing and antibody technology aimed at minimizing the risk of these events... - Pulmonary endothelium dependent vasodilation emerges after birth in miceRenato Faro
Cardiothoracic Pharmacology, UCCM and Thoracic Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, SW3 6LY, U K
Eur J Pharmacol 567:240-4. 2007..This approach can be used with genetically modified mice, which is important to further our understanding of the physiology in this area... - Transition from placental to air breathing stimulates haem-oxygenase-1 expression without functional consequence for pulmonary vascular adaptation in pigs and miceSalome J Stanford
Cardiothoracic Pharmacology, UCCM, The Royal Brompton and Harefield N H S Trust, Imperial College, National Heart and Lung Institute, Dovehouse Street, Sydney Street, London, UK
Br J Pharmacol 144:467-76. 2005..These data suggest that HO-1 expression at birth is a redundant response to oxidative stress in the lungs of healthy mammals. However, it remains possible that this pathway protects if complications occur during or after birth... - The PPARbeta/delta agonist GW0742 relaxes pulmonary vessels and limits right heart hypertrophy in rats with hypoxia-induced pulmonary hypertensionLouise S Harrington
Cardiothoracic Pharmacology, NHLI, Imperial College London, United Kingdom
PLoS ONE 5:e9526. 2010..However, none of these provide a cure and the clinical benefits of these drugs individually decline over time. There is, therefore, an urgent need to identify new treatment strategies for pulmonary hypertension... - Role of shear stress in endothelial cell morphology and expression of cyclooxygenase isoformsClaire M F Potter
Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, UK
Arterioscler Thromb Vasc Biol 31:384-91. 2011..The goal of this study was to examine the effect of chronic heterogeneous shear stress, applied using an orbital shaker, on endothelial cell morphology and the expression of cyclooxygenases 1 and 2... - Stronger inhibition by nonsteroid anti-inflammatory drugs of cyclooxygenase-1 in endothelial cells than platelets offers an explanation for increased risk of thrombotic eventsJane A Mitchell
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, Royal Brompton Hospital, Imperial College School of Medicine, London, UK
FASEB J 20:2468-75. 2006..The results reported here can offer an explanation for the apparent ability of NSAIDs and COX-2-selective inhibitors to increase the risk of myocardial infarction and stroke... - Pharmacology and therapeutic potential of interferonsPeter M George
Cardiothoracic Pharmacology, National Heart and Lung Institute NHLI, Imperial College, Dovehouse Street, London SW3 6LY, UK
Pharmacol Ther 135:44-53. 2012..Finally, we look to the future of interferon drug treatment, examining the potential for emerging therapies... - Intestinal injury and endotoxemia in children undergoing surgery for congenital heart diseaseNazima Pathan
Department of Paediatrics, Imperial College London, London, England, UK
Am J Respir Crit Care Med 184:1261-9. 2011..Children with congenital heart disease are at risk of gut barrier dysfunction and translocation of gut bacterial antigens into the bloodstream. This may contribute to inflammatory activation and organ dysfunction postoperatively... - Cigarette smoke activates human monocytes by an oxidant-AP-1 signaling pathway: implications for steroid resistanceMatthew J Walters
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, Imperial College London, National Heart and Lung Institute, Dovehouse Street, London, SW3 6LY, UK
Mol Pharmacol 68:1343-53. 2005..These observations add significantly to our understanding of smoke as an inflammatory stimulus that has implications for potential the development of treatments of smoking or related disease... - COX isoforms in the cardiovascular system: understanding the activities of non-steroidal anti-inflammatory drugsJane A Mitchell
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, National Heart and Lung Institute, Royal Brompton Hospital, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK
Nat Rev Drug Discov 5:75-86. 2006.... - Cyclooxygenase-2 acts as an endogenous brake on endothelin-1 release by human pulmonary artery smooth muscle cells: implications for pulmonary hypertensionStephen J Wort
Unit of Critical Care Medicine, Imperial College School of Medicine, Royal Brompton Hospital, London, United Kingdom
Mol Pharmacol 62:1147-53. 2002.... - Not so EEZE: the 'EDHF' antagonist 14, 15 epoxyeicosa-5(Z)-enoic acid has vasodilator properties in mesenteric arteriesLouise S Harrington
Unit of Critical Care Medicine, Royal Brompton Hospital, The National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London, SW3 6LY, UK
Eur J Pharmacol 506:165-8. 2004..These results illustrate an important pharmacological property of this antagonists, which is being increasingly used to study the nature of EDHF... - Type II nitric oxide synthase activity is cardio-protective in experimental sepsisSuzanna Price
Unit of Critical Care Medicine, Imperial College School of Medicine, Royal Brompton Hospital, Dovehouse Street, London SW3 6LY, UK
Eur J Pharmacol 472:111-8. 2003..These findings suggest that NOSII is cardio-protective in the heart in sepsis and explain why its inhibition in man led to increased mortality in a subpopulation of patients... - Effect of different interferonα2 preparations on IP10 and ET-1 release from human lung cellsRekha Badiger
Cardiothoracic Pharmacology, National Heart and Lung Institute NHLI, Imperial College, London, United Kingdom
PLoS ONE 7:e46779. 2012..Although rare, these adverse events can be severe and potentially life-threatening, emphasizing the need for simple biomarkers of IFN-induced lung toxicity... - Targeting PPAR receptors in the airway for the treatment of inflammatory lung diseaseMaria G Belvisi
Respiratory Pharmacology Group, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK
Br J Pharmacol 158:994-1003. 2009..In conclusion, PPARs are novel targets for lung disease and continued work with these ligands may result in a potential new treatment for chronic inflammatory lung diseases... - Elucidation of the temporal relationship between endothelial-derived NO and EDHF in mesenteric vesselsLouise S Harrington
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, The National Heart and Lung Institute, Imperial College, London, United Kingdom
Am J Physiol Heart Circ Physiol 293:H1682-8. 2007..These data show for the first time that EDHF is released transiently, whereas endothelial-derived NO is released in a sustained manner... - Scanning ion conductance microscopy: a convergent high-resolution technology for multi-parametric analysis of living cardiovascular cellsMichele Miragoli
Cardiovascular Science, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW36LY, UK
J R Soc Interface 8:913-25. 2011..In conclusion, SICM provides a highly informative multimodal imaging platform for functional analysis of the mechanisms of cardiovascular diseases, which should facilitate identification of novel therapeutic strategies... - Nitric oxide supports atrial function in sepsis: relevance to side effects of inhibitors in shockSusanna Price
Unit of Critical Care Medicine, Imperial College School of Medicine, National Heart and Lung Institute, Dovehouse Street, London, SW3 6LY, UK
Eur J Pharmacol 449:279-85. 2002..Our results suggest that myocardial contractility is maintained by NO production and that inhibitors may compromise cardiac output; this may explain the deleterious effects of NOS inhibition on cardiac function in clinical trials... - Novel role for P2X receptor activation in endothelium-dependent vasodilationLouise S Harrington
Unit of Critical Care Medicine, Royal Brompton Hospital, The National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London, SW3 6LY
Br J Pharmacol 143:611-7. 2004..These observations have important implications for our understanding of the role of purines in biological responses... - Role of prostacyclin versus peroxisome proliferator-activated receptor beta receptors in prostacyclin sensing by lung fibroblastsFerhana Y Ali
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, National Heart and Lung Institute, Imperial College, London, UK
Am J Respir Cell Mol Biol 34:242-6. 2006..This study is the first to identify PPARbeta as a potential therapeutic target for the treatment of pulmonary hypertension, which is important because orally active PPARbeta ligands have been developed for the treatment of dyslipidemia... - Cellular mechanisms of acetaminophen: role of cyclo-oxygenaseRuth Lucas
Cardiothoracic Pharmacology, UCCM, Royal Brompton Hospital, NHLI, Imperial College London, UK
FASEB J 19:635-7. 2005..Specifically, combining active site selectively with actions on enzyme oxidation state would allow for a broader range of tissue selective drugs... - Cyclooxygenases: new forms, new inhibitors, and lessons from the clinicTimothy D Warner
The William Harvey Research Institute, Barts and The London, Queen Mary s School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK
FASEB J 18:790-804. 2004..This review will discuss how the latest studies help us understand the roles of COX-1 and COX-2 and what clinically proven benefits the newer generation of COX-2-selective inhibitors offer.. - Effects of cyclooxygenase-1/cyclooxygenase-2 inhibition on leukocyte/endothelial cell interactions in the rat mesenterySara Calatayud
Unidad Mixta de Investigacion, Facultad de Medicina Hospital Clínico Universitario, Universidad de Valencia, Blasco Ibanez 17, 46010, Valencia, Spain
Eur J Pharmacol 440:71-7. 2002..Specific blockade of cyclooxygenase-1 or cyclooxygenase-2 does not induce any inflammatory event in the rat mesentery and the inflammatory response observed with non-selective NSAIDs seems to be due to the inhibition of both isoenzymes... - Cyclo-oxygenase-2 inhibitors and cardiovascular eventsTimothy D Warner
Lancet 360:1700-1. 2002 - Carbon monoxide inhibits endothelin-1 release by human pulmonary artery smooth muscle cellsSalome J Stanford
Unit of Critical Care, The Royal Brompton and Harefield NHS Trust, Imperial College School of Medicine, Sydney Street, London SW3 6NP, UK
Eur J Pharmacol 486:349-52. 2004..Under certain conditions, carbon monoxide appears to act as an endogenous break on endothelin-1 release... - Activation of peroxisome proliferator-activated receptors in human airway smooth muscle cells has a superior anti-inflammatory profile to corticosteroids: relevance for chronic obstructive pulmonary disease therapyHema J Patel
Respiratory Pharmacology Group, Department of Cardiothoracic Surgery, Faculty of Medicine, The National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom
J Immunol 170:2663-9. 2003..Hence, PPAR ligands might act as potential treatments in human respiratory diseases... - Endothelium-dependent relaxation and endothelial hyperpolarization by P2Y receptor agonists in rat-isolated mesenteric arteryHammit Mistry
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK
Br J Pharmacol 139:661-71. 2003..The mechanisms for potentiation of relaxation and hyperpolarization by ATPgammaS are unknown, but may indicate interactions between P2Y receptor subtypes... - HIF, stretching to get control of VEGFTimothy D Warner
The William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK
Clin Sci (Lond) 105:393-4. 2003....