Research Topics
Genomes and Genes | Stephen T HolgateSummaryAffiliation: University of Southampton Country: UK Publications
| Collaborators
|
Detail Information
Publications
The mechanisms, diagnosis, and management of severe asthma in adultsStephen T Holgate
AIR Division, Level D Centre Block, Southampton General Hospital, Southampton, UK
Lancet 368:780-93. 2006....
Trials and tribulations in identifying new biologic treatments for asthmaStephen T Holgate
Inflammation, Infection and Immunity Division, Sir Henry Wellcome Laboratories, Mail Point 810, Level F, South Block, Southampton General Hospital, Southampton SO16 6YD, UK
Trends Immunol 33:238-46. 2012..To achieve this goal, a different type of relationship is needed between academia and industry, and also within industry, to promote collaboration in the precompetitive space...
Innate and adaptive immune responses in asthmaStephen T Holgate
Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Southampton General Hospital, UK
Nat Med 18:673-83. 2012....
Asthma: a simple concept but in reality a complex diseaseStephen T Holgate
School of Medicine, University of Southampton, Southampton, UK
Eur J Clin Invest 41:1339-52. 2011..Over the 2 decades that followed, these drugs have been progressively improved by increasing their therapeutic index and duration of action...
Improving outcomes for asthma patients with allergic rhinitis: conclusions from the MetaForum conferencesDavid Price
Department of General Practice and Primary Care, University of Aberdeen, Foresterhill Health Centre, Westburn Road, Aberdeen AB25 2AY, UK
BMC Pulm Med 6:S7. 2006
Invited lecture: activation of the epithelial mesenchymal trophic unit in the pathogenesis of asthmaS T Holgate
Respiratory Cell and Molecular Biology Division, School of Medicine, Southampton General Hospital, Southampton, UK
Int Arch Allergy Immunol 124:253-8. 2001..This report describes a series of studies that identify aberrant epithelial mesenchymal signalling in the airways as an important event in maintaining inflammation and driving remodelling in response to environmental injury...
Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanismsS T Holgate
Allergy and Inflammation Research, Southampton General Hospital, Southampton SO16 6YD, UK
Eur Respir J 29:793-803. 2007....
Mechanisms of airway epithelial damage: epithelial-mesenchymal interactions in the pathogenesis of asthmaS T Holgate
Division of Infection, Inflammation and Repair, Mailpoint 810, Level D, Centre Block, Southampton General Hospital, Southampton SO16 6YD, UK
Eur Respir J Suppl 44:24s-29s. 2003
Consensus Group on New-Generation Antihistamines (CONGA): present status and recommendationsS T Holgate
Respiratory Cell and Molecular Biology, Infection, Inflammation, and Repair Division, School of Medicine, University of Southampton, UK
Clin Exp Allergy 33:1305-24. 2003
Epithelium dysfunction in asthmaStephen T Holgate
Allergy and Inflammation Research, Division of Infection, School of Medicine, Southampton General Hospital and the University of Southampton, Southampton, United Kingdom
J Allergy Clin Immunol 120:1233-44; quiz 1245-6. 2007....
The airway epithelium is central to the pathogenesis of asthmaStephen T Holgate
School of Medicine, Southampton General Hospital, Southampton, UK
Allergol Int 57:1-10. 2008....
A new look at the pathogenesis of asthmaStephen T Holgate
University of Southampton, Southampton General Hospital, UK
Clin Sci (Lond) 118:439-50. 2010..It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established...
Introduction: the anti-inflammatory role of cysteinyl leukotriene receptor antagonists in asthmaStephen T Holgate
Respiratory Division, University of Southampton School of Medicine, Southampton, United Kingdom
J Allergy Clin Immunol 111:S1-4. 2003
The role of the airway epithelium and its interaction with environmental factors in asthma pathogenesisStephen T Holgate
Infection, Inflammation and Immunity Division, School of Medicine, Southampton University, Southampton General Hospital, Southampton SO166YD, UK
Proc Am Thorac Soc 6:655-9. 2009..Viewing asthma primarily as an epithelial disease with adoption of a chronic wound scenario also provides a route to airway wall remodeling and the varying asthma phenotypes over the life course...
Has the time come to rethink the pathogenesis of asthma?Stephen T Holgate
University of Southampton, Hampshire, UK
Curr Opin Allergy Clin Immunol 10:48-53. 2010..However, ranges of approaches that have targeted this immunological component have so far been disappointing. Most asthma therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms...
Novel targets of therapy in asthmaStephen T Holgate
IIR Division, School of Medicine, Southampton General Hospital, Southampton, UK
Curr Opin Pulm Med 15:63-71. 2009..However, none of these therapies are specifically directed to the underlying causal pathways of asthma. In this review the role of selective inhibitors of the inflammatory cascade are presented with a particular emphasis on biologics...
Treatment strategies for allergy and asthmaStephen T Holgate
IIR Division, F Level, South Block, Southampton General Hospital, Southampton, SO16 6YD, UK
Nat Rev Immunol 8:218-30. 2008....
Asthma out of control? A structured review of recent patient surveysStephen T Holgate
Infection, Inflammation and Repair AIR Division, Level F, South Block, MP810, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK
BMC Pulm Med 6:S2. 2006..The primary goal of the present review was to assess patient perspectives on key issues in asthma and its management, as captured in patient surveys...
ADAM metallopeptidase domain 33 (ADAM33): identification and role in airways diseaseStephen T Holgate
Infection, Inflammation and Immunity Division, Southampton General Hospital, Southampton, UK
Drug News Perspect 23:381-7. 2010..These all point to ADAM33 being a key molecule in the development and progression of asthma by contributing to smooth muscle and vascular modeling and remodeling...
Efficacy and safety of etanercept in moderate-to-severe asthma: a randomised, controlled trialS T Holgate
School of Medicine, University of Southampton, III Division, Mail Point 810, Level F, South Block, Southampton General Hospital, Southampton, Hampshire, SO16 6YD, UK
Eur Respir J 37:1352-9. 2011..However, ETN treatment was a well-tolerated therapy. Studies in specific subsets of patients with asthma with longer-term follow-up may be needed to fully evaluate the clinical efficacy of ETN in this population...
ADAM33: a newly identified gene in the pathogenesis of asthmaStephen T Holgate
Infection, Inflammation, and Repair Division, School of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, Hampshire, SO16 6YD, UK
Immunol Allergy Clin North Am 25:655-68. 2005..For each of these genes, as is the case for ADAM33, determining their normal function(s) and how these become disordered in asthma is the future challenge...
Understanding the pathophysiology of severe asthma to generate new therapeutic opportunitiesStephen T Holgate
Division of Infection, Inflammation and Repair, School of Medicine, University of Southampton, Southampton General Hospital, UK
J Allergy Clin Immunol 117:496-506; quiz 507. 2006....
Anti-immunoglobulin E treatment with omalizumab in allergic diseases: an update on anti-inflammatory activity and clinical efficacyS T Holgate
Southampton General Hospital, Southampton, UK
Clin Exp Allergy 35:408-16. 2005..These impressive clinical data and the studies elucidating the anti-inflammatory profile of omalizumab also serve to emphasize the fundamental importance of IgE in the pathogenesis of allergic diseases...
The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammationStephen Holgate
RCMB Research Division, Southampton General Hospital, United Kingdom
J Allergy Clin Immunol 115:459-65. 2005....
The genetics of asthma: ADAM33 as an example of a susceptibility geneStephen T Holgate
Infection, Inflammation, and Repair Division, MP810, F Level, South Block, Southampton General Hospital, Southampton SO16 6YD, UK
Proc Am Thorac Soc 3:440-3. 2006....
Lessons learnt from the epidemic of asthmaS T Holgate
Allergy and Inflammation Research Division, Southampton General Hospital, Southampton, UK
QJM 97:247-57. 2004
Pathophysiology of asthma: what has our current understanding taught us about new therapeutic approaches?Stephen T Holgate
Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton General Hospital, Southampton, United Kingdom
J Allergy Clin Immunol 128:495-505. 2011....
Chronic fatigue syndrome: understanding a complex illnessStephen T Holgate
University of Southampton, Infection, Inflammation and Immunity Division, School of Medicine, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK
Nat Rev Neurosci 12:539-44. 2011..Nature Reviews Neuroscience asked four scientists involved in CFS research about their views on the condition, its causes and the future of research aimed at improving our understanding of this chronic illness...
Susceptibility genes in severe asthmaStephen T Holgate
Infection, Inflammation and Repair Division, MP810, F Level, South Block, Southampton General Hospital, Southampton, SO16 6YD, UK
Curr Allergy Asthma Rep 6:345-8. 2006..In this review, we bring together recent literature in the field of genetic influences over disease severity and discuss some of the clinical implications in terms of drug discovery and personalized medicine...
The sentinel role of the airway epithelium in asthma pathogenesisStephen T Holgate
Allergy and Inflammation Research, Division of Infection, Inflammation and Immunity, School of Medicine, Southampton University and General Hospital, Southampton, Hampshire, UK
Immunol Rev 242:205-19. 2011....
Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthmaS T Holgate
RCMB Research Division, Southampton General Hospital, Southampton, UK
Clin Exp Allergy 34:632-8. 2004..Patients with severe asthma are often inadequately controlled on existing anti-asthma therapy, constituting an unmet clinical need...
The epidemic of allergy and asthmaS T Holgate
Respiratory, Cell and Molecular Biology Research Division of the School of Medicine, University of Southampton, Southampton General Hospital, UK
Nature 402:B2-4. 1999....
Efficacy of omalizumab, an anti-immunoglobulin E antibody, in patients with allergic asthma at high risk of serious asthma-related morbidity and mortalityS Holgate
RCMB Research Division, Southampton General Hospital, UK
Curr Med Res Opin 17:233-40. 2001..The aim of the present study was to determine the efficacy of omalizumab in a subgroup of patients at high risk of serious asthma-related morbidity and mortality...
Epithelial-mesenchymal communication in the pathogenesis of chronic asthmaStephen T Holgate
Respiratory Cell and Molecular Biology, Infection, Inflammation and Repair Division, School of Medicine, University of Southampton, D Level Centre Block, Southampton General Hospital, Southampton SO16 6YD, UK
Proc Am Thorac Soc 1:93-8. 2004....
Characterization of ciliated bronchial epithelium 1, a ciliated cell-associated gene induced during mucociliary differentiationHajime Yoshisue
Infection, Inflammation, and Repair Division, University of Southampton School of Medicine, Southampton General Hospital, Southampton, United Kingdom
Am J Respir Cell Mol Biol 31:491-500. 2004..Regulated expression during differentiation and the subcellular localization of CBE1 suggest that it may play an important role in the differentiation and/or function of ciliated cells in human airways...
IFN-gamma-induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbationsPeter A B Wark
Brooke Laboratories, University of Southampton, Southampton, United Kingdom
J Allergy Clin Immunol 120:586-93. 2007..Rhinovirus-induced acute asthma is the most frequent trigger for asthma exacerbations...
IL-4 receptor alpha is an important modulator of IL-4 and IL-13 receptor binding: implications for the development of therapeutic targetsAllison Lynn Andrews
The Brooke Laboratories, Division of Infection, Inflammation, and Repair, Southampton General Hospital, UK
J Immunol 176:7456-61. 2006....
ADAM33 expression in asthmatic airways and human embryonic lungsHans Michael Haitchi
Roger Brooke Laboratories, Division of Infection, Inflammation, and Repair, and Human Genetics Division, School of Medicine, University of Southampton, Southampton General Hospital, United Kingdom
Am J Respir Crit Care Med 171:958-65. 2005..Polymorphic variation in ADAM33 (A Disintegrin And Metalloprotease) is strongly associated with asthma and bronchial hyperresponsiveness in different populations...
Cooperative effects of Th2 cytokines and allergen on normal and asthmatic bronchial epithelial cellsJames L Lordan
School of Medicine, Respiratory Cell and Molecular Biology Division, Southampton General Hospital, Southampton, United Kingdom
J Immunol 169:407-14. 2002....
Beta-catenin/T-cell factor-mediated transcription is modulated by cell density in human bronchial epithelial cellsMark D Steel
The Brooke Laboratories, School of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK
Int J Biochem Cell Biol 37:1281-95. 2005..Recognising that many chronic inflammatory disorders of the airways involve epithelial damage and repair, altered Wnt signalling might contribute to disease pathogenesis or progression...
Increased expression of p21(waf) cyclin-dependent kinase inhibitor in asthmatic bronchial epitheliumSarah M Puddicombe
The Brooke Laboratory, Division of Infection, Inflammation and Repair, School of Medicine, Southampton General Hospital, Southampton, United Kingdom
Am J Respir Cell Mol Biol 28:61-8. 2003..We conclude that p21(waf) overexpression in asthma influences cell proliferation and survival. This may cause abnormal repair responses that contribute to airway inflammation and remodeling...
Asthmatic bronchial epithelium is more susceptible to oxidant-induced apoptosisFabio Bucchieri
School of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom
Am J Respir Cell Mol Biol 27:179-85. 2002..This susceptibility may contribute to the rising trends in asthma associated with air pollution and diets low in antioxidants...
Epigenetic mechanisms silence a disintegrin and metalloprotease 33 expression in bronchial epithelial cellsYouwen Yang
Brooke Laboratories, Division of Infection, Inflammation and Repair, School of Medicine, University of Southampton, Southampton, United Kingdom
J Allergy Clin Immunol 121:1393-9, 1399.e1-14. 2008..Although considered to be a mesenchymal cell-specific gene, recent reports have suggested epithelial expression of ADAM33 in patients with severe asthma...
The splicing and fate of ADAM33 transcripts in primary human airways fibroblastsRobert M Powell
Brooke Laboratories, Division of Infection, School of Medicine, Southampton General Hospital, Southampton, UK
Am J Respir Cell Mol Biol 31:13-21. 2004..These findings demonstrate that ADAM33 exists in multiple isoforms, suggesting that it is a complex molecule that plays multiple roles within mesenchymal cells...
Defective epithelial barrier function in asthmaChang Xiao
Synairgen Research Ltd, Southampton General Hospital, Southampton, United Kingdom
J Allergy Clin Immunol 128:549-56.e1-12. 2011..The bronchial epithelium forms the interface with the external environment and is pivotally involved in controlling tissue homeostasis through provision of a physical barrier controlled by tight junction (TJ) complexes...
Double-stranded RNA induces disproportionate expression of thymic stromal lymphopoietin versus interferon-beta in bronchial epithelial cells from donors with asthmaLena Uller
The Brooke Laboratories, Sir Henry Wellcome Laboratories, South Block, Southampton General Hospital, Southampton SO16 6YD, UK
Thorax 65:626-32. 2010....
IL-13 receptor alpha 2: a regulator of IL-13 and IL-4 signal transduction in primary human fibroblastsAllison-Lynn Andrews
Brooke Laboratories, Division of Infection, Inflammation, and Repair, UK
J Allergy Clin Immunol 118:858-65. 2006..CLINICAL IMPLICATIONS: It appears that IL-13Ralpha2 might be a powerful suppressor of TH2-mediated responses and thus represents a potential therapeutic target for the treatment of asthma...
The discovery and role of ADAM33, a new candidate gene for asthmaJohn W Holloway
Human Genetics Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK
Expert Rev Mol Med 6:1-12. 2004..ADAM33 might play a key role in predisposing to the reduced lung function characteristic of asthma, possibly by influencing airway wall remodelling...
ADAM 33 and its association with airway remodeling and hyperresponsiveness in asthmaStephen T Holgate
Respiratory Cell and Molecular Biology Research Division, School of Medicine, University of Southampton, UK, University of Cambridge, UK
Clin Rev Allergy Immunol 27:23-34. 2004..The potential for therapeutic intervention with ADAM 33 is extremely attractive and further work will not only focus on the specific domains of ADAM 33, but also the mechanisms by which they lead to bronchial hyperreactivity...
Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirusPeter A B Wark
The Brooke Laboratories, University of Southampton, Southampton SO16 6YD, UK
J Exp Med 201:937-47. 2005..These data suggest a novel use for type I interferons in the treatment or prevention of virus-induced asthma exacerbations...
Cysteinyl leukotrienes synergize with growth factors to induce proliferation of human bronchial fibroblastsHajime Yoshisue
Division of Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton General Hospital, UK
J Allergy Clin Immunol 119:132-40. 2007..Cysteinyl leukotrienes (cys-LTs) are potent asthma-related mediators that function through their G protein-coupled receptors, cys-LT receptor type 1 (CysLT1R) and cys-LT receptor type 2 (CysLT2R)...
Effect of IL-13 receptor alpha2 levels on the biological activity of IL-13 variant R110QAllison Lynn Andrews
Infection, Inflammation and Repair Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK
J Allergy Clin Immunol 120:91-7. 2007..Recently a polymorphic variant of IL-13 (R110Q) has been shown to be associated with atopy...
Contribution of bronchial fibroblasts to the antiviral response in asthmaNicole Bedke
Division of Infection, Inflammation, and Repair, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom
J Immunol 182:3660-7. 2009..Their ability to support viral replication coupled with their vigorous proinflammatory response following infection may contribute to asthma exacerbations...
Induction of a disintegrin and metalloprotease 33 during embryonic lung development and the influence of IL-13 or maternal allergyHans Michael Haitchi
Division of Infection Inflammation and Immunity, Roger Brooke Laboratory, School of Medicine, University of Southampton, Southampton, UK
J Allergy Clin Immunol 124:590-7, 597.e1-11. 2009..ADAM33 is almost exclusively expressed in mesenchymal cells, including mesenchymal progenitors in developing lungs...
Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthmaRatko Djukanovic
Respiratory Cell and Molecular Biology, Division of Infection, Inflammation, and Repair, University of Southampton, Southampton, UK
Am J Respir Crit Care Med 170:583-93. 2004..The lack of effect of omalizumab on methacholine responsiveness suggests that IgE or eosinophils may not be causally linked to airway hyperresponsiveness to methacholine in mild to moderate asthma...
Roles of cysteinyl leukotrienes in airway inflammation, smooth muscle function, and remodelingStephen T Holgate
Respiratory, Cell, and Molecular Biology Research Division, University of Southampton School of Medicine, Southampton, UK
J Allergy Clin Immunol 111:S18-34; discussion S34-6. 2003....
Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmaticsM L Seymour
Division of Respiratory Cell and Molecular Biology, Southampton General Hospital, Southampton, United Kingdom
Am J Respir Crit Care Med 164:2051-6. 2001..Inverse correlations between PEF and 5-LO(+) cell counts link increased expression of 5-LO pathway enzymes in eosinophils and macrophages within the bronchial mucosa to deterioration of lung function during seasonal allergen exposure...
Regulation of a disintegrin and metalloprotease-33 expression by transforming growth factor-βYouwen Yang
Southampton General Hospital, Southampton, UK
Am J Respir Cell Mol Biol 46:633-40. 2012..This may provide a mechanism for fine regulation of levels of ADAM33 expression in fibroblasts, and may self-limit TGF-β(2)-induced ectodomain shedding of ADAM33...
Exogenous IFN-β has antiviral and anti-inflammatory properties in primary bronchial epithelial cells from asthmatic subjects exposed to rhinovirusJulie A Cakebread
Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine and National Institute for Health Research Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, United Kingdom
J Allergy Clin Immunol 127:1148-54.e9. 2011....
Autocrine ligands for the epidermal growth factor receptor mediate interleukin-8 release from bronchial epithelial cells in response to cigarette smokeAudrey Richter
Respiratory Cell and Molecular Biology Division, School of Medicine, Southampton General Hospital, United Kingdom
Am J Respir Cell Mol Biol 27:85-90. 2002..Our data indicate that secretion of IL-8 in response to CSE is dependent on EGFR activation and that autocrine production of TGF-alpha makes a substantial contribution to this response...
NF-kappa B and TNF-alpha: a positive autocrine loop in human lung mast cells?William R Coward
Division of Infection, Inflammation and Repair, School of Medicine, Southampton General Hospital, United Kingdom
J Immunol 169:5287-93. 2002....
Human bronchial fibroblasts express the 5-lipoxygenase pathwayAnna J James
Division of Infection, Inflammation and Repair IIR, University of Southampton, School of Medicine, Southampton General Hospital, Southampton, SO16 6YD, UK
Respir Res 7:102. 2006..Fibroblast activity is influenced by members of the leukotriene family of bronchoconstrictor and inflammatory mediators, but it is not known whether human bronchial fibroblasts can synthesize leukotrienes...
Airway remodeling in asthma: new insightsDonna E Davies
Brooke Laboratories, Division of Infection, Inflammation and Repair, School of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK
J Allergy Clin Immunol 111:215-25; quiz 226. 2003....
Association of tumor necrosis factor-alpha polymorphisms and ozone-induced change in lung functionIan A Yang
Asthma Genetics Laboratory, Human Genetics Division, University of Southampton, United Kingdom
Am J Respir Crit Care Med 171:171-6. 2005..The results of this study support TNF as a genetic factor for susceptibility to ozone-induced changes in lung function in humans, and has potential implications for stratifying health risks of air pollution...
The soluble form of a disintegrin and metalloprotease 33 promotes angiogenesis: implications for airway remodeling in asthmaIlaria Puxeddu
Division of Infection, Inflammation, and Repair, School of Medicine, Southampton General Hospital, University of Southampton, Southampton, United Kingdom
J Allergy Clin Immunol 121:1400-6, 1406.e1-4. 2008..A disintegrin and metalloprotease (ADAM)-33 is a susceptibility gene for asthma and chronic obstructive pulmonary disease whose function remains unknown...
The cysteinyl-leukotriene type 1 receptor polymorphism 927T/C is associated with atopy severity but not with asthmaL Hao
Division of Human Genetics, University of Southampton School of Medicine, Southampton, UK
Clin Exp Allergy 36:735-41. 2006..We screened the CYSLTR1 gene on chromosome Xq13-21 for coding region polymorphisms, and investigated their associations with allergy and asthma...
Genetic and environmental influences on airway inflammation in asthmaS T Holgate
University Medicine, Southampton General Hospital, UK
Int Arch Allergy Immunol 107:29-33. 1995..These latter findings, being more evident in severe chronic disease, suggest that the 'formed' airway elements are also important in mediating the ongoing inflammation characteristic of asthma...
Induction of the epidermal growth factor receptor and its ligands in nasal epithelium by ozoneRiccardo Polosa
Respiratory Cell and Moleculat Biology Division, School of Medicine, Southampton General Hospital, Southampton, United Kingdom
J Allergy Clin Immunol 113:120-6. 2004..CONCLUSION: These data suggest that the ozone-induced increase in EGFR expression observed in vivo is indirect, perhaps mediated by neutrophil-derived TNF-alpha...
GeneticsJohn W Holloway
Human Genetics, Southampton General Hospital, University of Southampton, Southampton, UK
Chem Immunol Allergy 84:1-35. 2004
Polymorphisms in the interleukin-4 and interleukin-4 receptor alpha chain genes confer susceptibility to asthma and atopy in a Caucasian populationB Beghe
Divisions of Human Genetics Infection, Inflammation and Repair, School of Medicine, University of Southampton, UK
Clin Exp Allergy 33:1111-7. 2003..IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype...
Inflammatory cytokines can enhance CD44-mediated airway epithelial cell adhesion independently of CD44 expressionShih Hsing Leir
Respiratory Cell and Molecular Biology, Infection Immunity and Repair Division, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK
Am J Physiol Lung Cell Mol Physiol 285:L1305-11. 2003..These data indicate that CD44 is important for bronchial epithelial cell binding to HA and that cytokines known to be expressed in inflammation can increase HA binding independently of the level of CD44 expression...
Dynamics of pro-inflammatory and anti-inflammatory cytokine release during acute inflammation in chronic obstructive pulmonary disease: an ex vivo studyTillie Louise Hackett
School of Biological Sciences, University of Southampton, Southampton, UK
Respir Res 9:47. 2008..The aim of this study was to asses the kinetics of cytokine release from COPD parenchymal explants using an ex vivo model of lipopolysaccharide (LPS) induced acute inflammation...
Genetics of allergic diseaseJohn W Holloway
Division of Infection, Inflammation and Immunity, School of Medicine, University of Southampton, Southampton, United Kingdom
J Allergy Clin Immunol 125:S81-94. 2010....
The role of the epidermal growth factor receptor in sustaining neutrophil inflammation in severe asthmaL M Hamilton
Division of Infection, Inflammation and Repair, School of Medicine, University of Southampton, UK
Clin Exp Allergy 33:233-40. 2003..Although the EGFR is involved in epithelial growth and differentiation, it is unknown whether it also contributes to the inflammatory response in asthma...
Effect of desloratadine and loratadine on rhinovirus-induced intercellular adhesion molecule 1 upregulation and promoter activation in respiratory epithelial cellsA Papi
University Medicine, University of Southampton, Southampton, UK
J Allergy Clin Immunol 108:221-8. 2001..CONCLUSION: These effects are unlikely to be mediated by H(1)-receptor antagonism and suggest a novel mechanism of action that may be important for the therapeutic control of virus-induced asthma exacerbations...
Interaction of inhaled LTC4 with histamine and PGD2 on airway caliber in asthmaG D Phillips
Immunopharmacology Group, Southampton General Hospital, United Kingdom
J Appl Physiol 66:304-12. 1989..05) but not for FEV1 (P less than 0.05). We conclude that inhaled LTC4 interacts synergistically with histamine and PGD2 and that this effect, although small, may be a relevant interaction in asthma...
Kinetic analysis of the interleukin-13 receptor complexAllison Lynn Andrews
Infection, Inflammation and Repair Division, School of Medicine, University of Southampton, 97 Tremona Rd, Southampton General Hospital, Southampton SO16 6YD, United Kingdom
J Biol Chem 277:46073-8. 2002....
Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled studyMichael J Radcliffe
School of Medicine, Infection Inflammation and Repair Research Division, University of Southampton, Southampton General Hospital, Southampton SO16 6YD
BMJ 327:251-4. 2003..To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy...
Expression of c-erbB receptors and ligands in the bronchial epithelium of asthmatic subjectsRiccardo Polosa
School of Medicine, Division of Respiratory Cell and Molecular Biology, Southampton General Hospital, Southampton, United Kingdom
J Allergy Clin Immunol 109:75-81. 2002....
PLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function declineSheila J Barton
Division of Infection, Inflammation and Immunity, School of Medicine, University of Southampton, Southampton, United Kingdom
J Allergy Clin Immunol 123:1391-400.e17. 2009..Several studies have suggested that chromosome 19q13.1-3 contains asthma susceptibility genes...
The effect of inhaled 15-(s)-hydroxyeicosatetraenoic acid (15-HETE) on airway calibre and non-specific responsiveness in normal and asthmatic human subjectsC K Lai
Immunopharmacology Group, Southampton General Hospital, UK
Eur Respir J 3:38-45. 1990..41-fold of baseline after diluent (p less than 0.01) compared with a 1.1-fold increase after 15-HETE, p less than 0.01). These data suggest 15-HETE may play an autacoid role in airway function...
Peripheral blood CD4+ and CD8+ T cell type 1 and type 2 cytokine production in atopic asthmatic and normal subjectsS-H Cho
University Medicine, Southampton General Hospital, Southampton, UK
Clin Exp Allergy 32:427-33. 2002....
Altered protein tyrosine phosphorylation in asthmatic bronchial epitheliumL M Hamilton
The Brooke Laboratories, Mailpoint 888, Southampton General Hospital, Southampton, SO16 6YD, UK
Eur Respir J 25:978-85. 2005..The epidermal growth factor receptor and/or other tyrosine kinase pathways may contribute to persistent, corticosteroid-unresponsive inflammation in severe asthma...
Inhibition of adenosine 5'-monophosphate- and methacholine-induced bronchoconstriction in asthma by inhaled frusemideR Polosa
Dept of Immunopharmacology, Southampton General Hospital, UK
Eur Respir J 3:665-72. 1990..Its more potent activity against AMP and other bronchoconstrictor stimuli, that are considered to involve mast cell mediators, suggests an additional action on mast cell functions possibly at the level of the Ca++/Mg(++)-ATPase...
Nedocromil sodium is more potent than sodium cromoglycate against AMP-induced bronchoconstriction in atopic asthmatic subjectsR Richards
Medicine I, Level D, Centre Block, Southampton General Hospital, U K
Clin Exp Allergy 19:285-91. 1989..9 (FEV1) and 8.0 (Vmax30) times more potent than SCG (P less than 0.001). In conclusion, both drugs inhibit the bronchoconstrictor response to inhaled AMP, and nedocromil is at least 4-8 times more potent than SCG...
The effects of Mycobacterium vaccae on allergen-induced airway responses in atopic asthmaL Camporota
Division of Respiratory Cell and Molecular Biology, Southampton General Hospital, Southampton, UK
Eur Respir J 21:287-93. 2003..07). This study shows a trend toward significance for the effects of heat-killed Mycobacterium vaccae (SRL172) on allergen-induced airway responses. Further clinical trials, involving multiple dosing, are needed...
Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian populationI Sayers
Divisions of Human Genetics Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton General Hospital, Tremona Road, Southampton, UK
Clin Exp Allergy 33:1103-10. 2003..5-Lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) are essential for cysteinyl-leukotriene (cys-LT) production, critical mediators in asthma...
Increased expression of inducible nitric oxide synthase and cyclo-oxygenase-2 in the airway epithelium of asthmatic subjects and regulation by corticosteroid treatmentA E Redington
University Medicine, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
Thorax 56:351-7. 2001..We hypothesised that the in vivo expression of iNOS and COX-2 in the airways would be increased in asthma, and that these cytokine inducible enzymes may represent targets for regulation by corticosteroid treatment...
Signal transducer and activator of transcription 6 (STAT-6) expression and function in asthmatic bronchial epitheliumR E Mullings
Division of Respiratory Cell and Molecular Biology, School of Medicine, Southampton General Hospital, United Kingdom
J Allergy Clin Immunol 108:832-8. 2001..Asthma is associated with increased production of IL-4 and IL-13...
Interpatient variability in rates of asthma progression: can genetics provide an answer?John W Holloway
Division of Infection, Inflammation and Repair, School of Medicine, University of Southampton, Southampton, United Kingdom
J Allergy Clin Immunol 121:573-9. 2008....
A look at the pathogenesis of asthma: the need for a change in directionStephen T Holgate
Infection, Inflammation and Immunity Division, Southampton General Hospital, School of Medicine, University of Southampton, Southampton, United Kingdom
Discov Med 9:439-47. 2010....
Cytoplasmic tail of IL-13Ralpha2 regulates IL-4 signal transductionAllison Lynn Andrews
School of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK
Biochem Soc Trans 37:873-6. 2009..The receptor has more complicated functions than a simple decoy receptor. In this review, we discuss newly revealed functions of IL-13Ralpha2...
Using genetics to predict the natural history of asthma?John W Holloway
Division of Infection, Inflammation and Immunity, School of Medicine, University of Southampton, Southampton, UK
J Allergy Clin Immunol 126:200-9; quiz 210-1. 2010....
The epithelium takes centre stage in asthma and atopic dermatitisStephen T Holgate
School of Medicine, University of Southampton, Southampton, UK, SO16 6YD
Trends Immunol 28:248-51. 2007..Induction of TSLP production occurs through the activation of epithelial Toll-like receptors to provide an important new link between innate immunity and allergic disease...
Rethinking the pathogenesis of asthmaStephen T Holgate
III Division, School of Medicine, University of Southampton, Southampton S016 61D, UK
Immunity 31:362-7. 2009..It may be worthwhile to focus on increasing the resilience of the airways to environmental insults in addition to improving strategies that modify adaptive immunity or suppress inflammation...
TGF-beta isoform release and activation during in vitro bronchial epithelial wound repairWilliam J Howat
Division of Respiratory, Cell and Molecular Biology, School of Medicine, University of Southampton, United Kingdom
Am J Physiol Lung Cell Mol Physiol 282:L115-23. 2002..A faster repair may be advantageous in preventing access of environmental agents to the internal milieu of the lung although the production of active TGF-beta molecules may augment subepithelial fibrosis...
Targeting adenosine receptors: novel therapeutic targets in asthma and chronic obstructive pulmonary diseaseSteuart Rorke
Division of Respiratory Cell and Molecular Biology, University of Southampton School of Medicine, Southampton General Hospital, Southampton, UK
Am J Respir Med 1:99-105. 2002....
ADAM33: a novel therapeutic target for asthmaRobert M Powell
Expert Opin Ther Targets 7:485-94. 2003..The identification of ADAM33 as a major risk factor involved in the pathogenesis of BHR and airway wall remodelling provides insight into the pathogenesis of asthma and represents a novel therapeutic target...
Role of tumor necrosis factor alpha in asthmaK Suresh Babu
Respiratory Cell and Molecular Biology Infection, Inflammation and Repair, Southampton General Hospital, Level D, Centre Block, Mailpoint 810, Southampton SO16 6YD, UK
Immunol Allergy Clin North Am 24:583-97, v-vi. 2004..This article examines the role of TNF-alpha in asthma and the effects of blocking TNF-alpha as a possible therapeutic option in patients with severe corticosteroid-dependent asthma...
Newer therapies for asthma: a focus on anti-IgEK Suresh Babu
Respiratory Cell and Molecular Biology, Southampton General Hospital, UK
Indian J Chest Dis Allied Sci 44:107-15. 2002..This review gives a brief overview of the newer therapies under investigation with special reference to omalizumab in the treatment of allergic asthma...
Rhinovirus is not detectable in peripheral lung tissue after asthma deathMark W Watson
Respiratory Cell and Molecular Biology Research Division, University of Southampton, Southampton, UK
Respirology 8:234-8. 2003..Alternatively, RV may not extend to peripheral airways and more proximal tissue sampling or PCR assays for other viruses may be required to determine an association between viral respiratory tract infection and fatal asthma...
