Ian Adcock

Summary

Affiliation: Imperial College
Country: UK

Publications

  1. ncbi request reprint Anti-inflammatory mechanisms of glucocorticoids targeting granulocytes
    Gaetano Caramori
    Department of Thoracic Medicine, National Heart and Lung Institute at Imperial College School of Science, Technology and Medicine, Dovehouse Street, London, SW3 6LY, UK
    Curr Drug Targets Inflamm Allergy 4:455-63. 2005
  2. doi request reprint New targets for drug development in asthma
    Ian M Adcock
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
    Lancet 372:1073-87. 2008
  3. pmc Statins as potential therapeutic drug for asthma?
    Cheng Yuan
    Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, China
    Respir Res 13:108. 2012
  4. doi request reprint Strategies for improving the efficacy and therapeutic ratio of glucocorticoids
    Ian M Adcock
    Airways Disease, National Heart and Lung Institute, Imperial College London, SW3 6LY, UK
    Curr Opin Pharmacol 12:246-51. 2012
  5. pmc STAT6 expression in T cells, alveolar macrophages and bronchial biopsies of normal and asthmatic subjects
    Katsuyuki Tomita
    Department of Respiratory Medicine and Allergology, Kinki University School of Medicine, Osaka, Japan
    J Inflamm (Lond) 9:5. 2012
  6. pmc Exhaled carbon monoxide in asthmatics: a meta-analysis
    Jingying Zhang
    Department of Respiratory Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
    Respir Res 11:50. 2010
  7. pmc New drugs targeting Th2 lymphocytes in asthma
    Gaetano Caramori
    Dipartimento di Medicina Clinica e Sperimentale, Centro di Ricerca su Asma e BPCO, Universita di Ferrara, Ferrara, Italy
    J Occup Med Toxicol 3:S6. 2008
  8. pmc Modulation of LPS stimulated NF-kappaB mediated Nitric Oxide production by PKCepsilon and JAK2 in RAW macrophages
    Edward Jones
    School of Health and Biosciences, University of East London, London, UK
    J Inflamm (Lond) 4:23. 2007
  9. pmc Cigarette Smoke Exposure Alters mSin3a and Mi-2alpha/beta Expression; implications in the control of pro-inflammatory gene transcription and glucocorticoid function
    John A Marwick
    Section of Airways Disease, National Heart and Lung Institute, Imperial College London, UK
    J Inflamm (Lond) 7:33. 2010
  10. pmc Histone deacetylase inhibitors induce apoptosis in human eosinophils and neutrophils
    Hannu Kankaanranta
    The Immunopharmacology Research Group, Medical School, FIN 33014, University of Tampere and Research Unit, Tampere University Hospital, Tampere, Finland
    J Inflamm (Lond) 7:9. 2010

Detail Information

Publications108 found, 100 shown here

  1. ncbi request reprint Anti-inflammatory mechanisms of glucocorticoids targeting granulocytes
    Gaetano Caramori
    Department of Thoracic Medicine, National Heart and Lung Institute at Imperial College School of Science, Technology and Medicine, Dovehouse Street, London, SW3 6LY, UK
    Curr Drug Targets Inflamm Allergy 4:455-63. 2005
    ..We summarize these known mechanisms at the end of this review...
  2. doi request reprint New targets for drug development in asthma
    Ian M Adcock
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
    Lancet 372:1073-87. 2008
    ..Although a cure is unlikely to be developed in the near future, a greater understanding of disease mechanisms could bring such a situation nearer to reality...
  3. pmc Statins as potential therapeutic drug for asthma?
    Cheng Yuan
    Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, China
    Respir Res 13:108. 2012
    ..The aim of this study is to determine whether statins are beneficial for asthma administration, and explore the potential covariables that may affect their clinical effectiveness...
  4. doi request reprint Strategies for improving the efficacy and therapeutic ratio of glucocorticoids
    Ian M Adcock
    Airways Disease, National Heart and Lung Institute, Imperial College London, SW3 6LY, UK
    Curr Opin Pharmacol 12:246-51. 2012
    ....
  5. pmc STAT6 expression in T cells, alveolar macrophages and bronchial biopsies of normal and asthmatic subjects
    Katsuyuki Tomita
    Department of Respiratory Medicine and Allergology, Kinki University School of Medicine, Osaka, Japan
    J Inflamm (Lond) 9:5. 2012
    ..abstract:..
  6. pmc Exhaled carbon monoxide in asthmatics: a meta-analysis
    Jingying Zhang
    Department of Respiratory Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
    Respir Res 11:50. 2010
    ..The purpose of this meta-analysis is to determine whether eCO is elevated in asthmatics, is regulated by steroid treatment and reflects disease severity and control...
  7. pmc New drugs targeting Th2 lymphocytes in asthma
    Gaetano Caramori
    Dipartimento di Medicina Clinica e Sperimentale, Centro di Ricerca su Asma e BPCO, Universita di Ferrara, Ferrara, Italy
    J Occup Med Toxicol 3:S6. 2008
    ..Some of these new Th2-oriented strategies may in the future not only control symptoms and modify the natural course of asthma, but also potentially prevent or cure the disease...
  8. pmc Modulation of LPS stimulated NF-kappaB mediated Nitric Oxide production by PKCepsilon and JAK2 in RAW macrophages
    Edward Jones
    School of Health and Biosciences, University of East London, London, UK
    J Inflamm (Lond) 4:23. 2007
    ..Here, we examine the role of protein kinase C isoforms and janus activated kinase 2 (JAK2) activation in NF-kappaB activation and LPS-stimulated NO production...
  9. pmc Cigarette Smoke Exposure Alters mSin3a and Mi-2alpha/beta Expression; implications in the control of pro-inflammatory gene transcription and glucocorticoid function
    John A Marwick
    Section of Airways Disease, National Heart and Lung Institute, Imperial College London, UK
    J Inflamm (Lond) 7:33. 2010
    ..However, the impact of cigarette smoke exposure on the expression of mSin3a and Mi2alpha/beta and their role in glucocorticoid responsiveness is unknown...
  10. pmc Histone deacetylase inhibitors induce apoptosis in human eosinophils and neutrophils
    Hannu Kankaanranta
    The Immunopharmacology Research Group, Medical School, FIN 33014, University of Tampere and Research Unit, Tampere University Hospital, Tampere, Finland
    J Inflamm (Lond) 7:9. 2010
    ..The aim of the present study was to explore the effects of HDAC inhibitors on apoptosis in human eosinophils and neutrophils...
  11. ncbi request reprint Kinase inhibitors and airway inflammation
    Ian M Adcock
    Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, SW3, 6LY, United Kingdom
    Eur J Pharmacol 533:118-32. 2006
    ....
  12. ncbi request reprint New insights into the molecular mechanisms of corticosteroids actions
    Ian M Adcock
    Cell and Molecular Biology, Airways Disease Section, National Heart and Lung Institute, Imperial College London, UK
    Curr Drug Targets 7:649-60. 2006
    ..Therapies targeting these aspects of the glucocorticoid receptor activation pathway may reverse steroid resistance in patients with chronic obstructive pulmonary disease...
  13. pmc Epigenetics and airways disease
    Ian M Adcock
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, UK
    Respir Res 7:21. 2006
    ..These changes, despite being heritable and stably maintained, are also potentially reversible and there is scope for the development of 'epigenetic therapies' for disease...
  14. ncbi request reprint Glucocorticoid pathways in chronic obstructive pulmonary disease therapy
    Ian M Adcock
    Cell and Molecular Biology, Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK
    Proc Am Thorac Soc 2:313-9; discussion 340-1. 2005
    ..Therapies targeting these aspects of the glucocorticoid receptor activation pathway may reverse steroid resistance in patients with chronic obstructive pulmonary disease...
  15. ncbi request reprint Redox regulation of histone deacetylases and glucocorticoid-mediated inhibition of the inflammatory response
    Ian M Adcock
    Thoracic Medicine, National Heart and Lung Institute, Imperial College London, London, UK
    Antioxid Redox Signal 7:144-52. 2005
    ..This may account for the lack of glucocorticoid sensitivity in patients with chronic obstructive pulmonary disease. Antioxidants should reduce the inflammation and restore glucocorticoid sensitivity in these subjects...
  16. ncbi request reprint Chemokine receptor inhibitors as a novel option in treatment of asthma
    Ian M Adcock
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, UK
    Curr Drug Targets Inflamm Allergy 3:257-61. 2004
    ..Furthermore, it is possible that early treatment with these agents may prevent the disease from becoming established...
  17. ncbi request reprint Kinase targets and inhibitors for the treatment of airway inflammatory diseases: the next generation of drugs for severe asthma and COPD?
    Ian M Adcock
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK
    BioDrugs 18:167-80. 2004
    ....
  18. ncbi request reprint Steroid resistance in asthma: a major problem requiring novel solutions or a non-issue?
    Ian M Adcock
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK
    Curr Opin Pharmacol 4:257-62. 2004
    ..However, management of those few patients with true steroid resistance will require novel therapies tailored to specific subgroups of patients...
  19. ncbi request reprint Glucocorticoids: new mechanisms and future agents
    Ian M Adcock
    Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse St, London SW3 6LY, UK
    Curr Allergy Asthma Rep 3:249-57. 2003
    ..This might have important clinical implications, leading to a better understanding of the inflammatory mechanisms of many diseases and might signal the development of new anti-inflammatory treatments in the future...
  20. ncbi request reprint Abnormal histone acetylase and deacetylase expression and function in lung inflammation
    I M Adcock
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, UK
    Inflamm Res 55:311-21. 2006
    ..Histone modifications, despite being heritable and stably maintained, are also potentially reversible and there is scope for the development of "epigenetic therapies" for disease...
  21. ncbi request reprint Histone deacetylase inhibitors as novel anti-inflammatory agents
    Ian M Adcock
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse St, London SW3 6LY, UK
    Curr Opin Investig Drugs 7:966-73. 2006
    ..More evidence is required concerning the long-term safety of these agents, for example, lung destruction, and in comparison with currently used therapies...
  22. doi request reprint Chronic obstructive pulmonary disease and lung cancer: new molecular insights
    Ian M Adcock
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
    Respiration 81:265-84. 2011
    ....
  23. pmc Differential patterns of histone acetylation in inflammatory bowel diseases
    Loukia G Tsaprouni
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, SW3 6LY, UK
    J Inflamm (Lond) 8:1. 2011
    ..Enhanced acetylation of H4K5 and K16 was seen in the PP. These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation...
  24. ncbi request reprint Mechanisms of corticosteroid resistance in severe asthma and chronic obstructive pulmonary disease (COPD)
    Ian M Adcock
    National Heart and Lung Institute, Imperial College London, UK
    Curr Pharm Des 16:3554-73. 2010
    ....
  25. doi request reprint Molecular mechanisms of corticosteroid resistance
    Ian M Adcock
    National Heart and Lung Institute, Imperial College London, Dovehouse St, London SW3 6LY, UK
    Chest 134:394-401. 2008
    ..Understanding the molecular mechanisms of GR action, and inaction, may lead to the development of new antiinflammatory drugs or may reverse the relative steroid insensitivity that is characteristic of patients with these diseases...
  26. ncbi request reprint Corticosteroid-insensitive asthma: molecular mechanisms
    I M Adcock
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK
    J Endocrinol 178:347-55. 2003
    ..Thus, elucidation of the cause for the relative lack of corticosteroid response in this subgroup of asthmatic individuals may have important implications for other diseases...
  27. ncbi request reprint Steroid resistance in asthma: mechanisms and treatment options
    Ian M Adcock
    Cell and Molecular Biology, Airways Disease Section, National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK
    Curr Allergy Asthma Rep 8:171-8. 2008
    ....
  28. doi request reprint Overcoming steroid unresponsiveness in airways disease
    Ian M Adcock
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK
    Biochem Soc Trans 37:824-9. 2009
    ..Understanding the molecular mechanisms of GR action, and inaction, may lead to the development of new anti-inflammatory drugs or reverse the relative corticosteroid-insensitivity that is characteristic of these diseases...
  29. ncbi request reprint Epigenetic regulation of airway inflammation
    Ian M Adcock
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
    Curr Opin Immunol 19:694-700. 2007
    ..Targeting specific enzymes involved in this process may lead to new therapeutic agents, in particular, in situations where current anti-inflammatory therapies are currently suboptimal...
  30. pmc HDAC inhibitors as anti-inflammatory agents
    I M Adcock
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
    Br J Pharmacol 150:829-31. 2007
    ..Although there are concerns over the long-term safety of these agents, they may prove useful particularly in situations where current anti-inflammatory therapies are suboptimal...
  31. ncbi request reprint Histone deacetylation: an important mechanism in inflammatory lung diseases
    Ian M Adcock
    National Heart and Lung Institute, Imperial College London, UK
    COPD 2:445-55. 2005
    ..The modulation of HAT/HDAC activity may lead to the development of novel anti-inflammatory approaches to inflammatory lung diseases that are currently difficult to treat...
  32. doi request reprint Hydrogen peroxide prolongs nuclear localization of NF-kappaB in activated cells by suppressing negative regulatory mechanisms
    Karine Enesa
    British Heart Foundation Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, W12 ONN, United Kingdom
    J Biol Chem 283:18582-90. 2008
    ..We conclude that H(2)O(2) prolongs NF-kappaB activation in co-stimulated cells by suppressing the negative regulatory functions of Cezanne and IkappaBalpha...
  33. pmc Relative corticosteroid insensitivity of peripheral blood mononuclear cells in severe asthma
    Mark Hew
    National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK
    Am J Respir Crit Care Med 174:134-41. 2006
    ..We hypothesized that this poor response is associated with a reduced effect of corticosteroids to inhibit cytokine release from activated peripheral blood mononuclear cells (PBMCs)...
  34. pmc Induction and regulation of matrix metalloproteinase-12 in human airway smooth muscle cells
    Shaoping Xie
    Experimental Studies, National Heart and Lung Institute, Imperial College, London, UK
    Respir Res 6:148. 2005
    ..We investigated whether human airway smooth muscle cells could express and secrete MMP-12, thereby participating in the pathogenesis of airway inflammatory diseases...
  35. ncbi request reprint p65-activated histone acetyltransferase activity is repressed by glucocorticoids: mifepristone fails to recruit HDAC2 to the p65-HAT complex
    K Ito
    Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, Dovehouse St, London SW3 6LY, United Kingdom
    J Biol Chem 276:30208-15. 2001
    ..These data also suggest that pharmacological manipulation of specific histone acetylation status is a potentially useful approach for the treatment of inflammatory diseases...
  36. pmc Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1beta-induced histone H4 acetylation on lysines 8 and 12
    K Ito
    Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom
    Mol Cell Biol 20:6891-903. 2000
    ..This further suggests that pharmacological manipulation of of specific histone acetylation status is a potentially useful approach for the treatment of inflammatory diseases...
  37. pmc A model of chronic inflammation and pulmonary emphysema after multiple ozone exposures in mice
    Kostas Triantaphyllopoulos
    Experimental Studies Unit, Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
    Am J Physiol Lung Cell Mol Physiol 300:L691-700. 2011
    ..Exposure of mice to ozone for 6 wk induced a chronic inflammatory process, with alveolar enlargement and damage linked to epithelial apoptosis and increased protease expression...
  38. ncbi request reprint Glucocorticoid-regulated transcription factors
    I M Adcock
    Thoracic Medicine, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Dovehouse Street, London SW3 6LY, UK
    Pulm Pharmacol Ther 14:211-9. 2001
    ....
  39. ncbi request reprint Cross-talk between pro-inflammatory transcription factors and glucocorticoids
    I M Adcock
    Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Science, Technology and Medicine, London, United Kingdom
    Immunol Cell Biol 79:376-84. 2001
    ..This suggests that cross-talk between pro- and anti-inflammatory transcription factors may modulate activation of the transcriptional complex and thereby reduce steroid actions...
  40. ncbi request reprint Pharmacology of airway inflammation in asthma and COPD
    Gaetano Caramori
    Department of Thoracic Medicine, National Heart and Lung Institute at Imperial College School of Science, Technology and Medicine, Dovehouse Street, SW3 6LY, London, UK
    Pulm Pharmacol Ther 16:247-77. 2003
    ..We review the current status of some of these new potential drugs...
  41. pmc Hydrogen sulfide inhibits proliferation and release of IL-8 from human airway smooth muscle cells
    Mark M Perry
    Experimental Studies, National Heart and Lung Institute, Imperial College London, London, United Kingdom
    Am J Respir Cell Mol Biol 45:746-52. 2011
    ..Therefore, regulation of H(2)S may represent a novel approach to controlling ASM proliferation and cytokine release that is found in patients with asthma...
  42. doi request reprint Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction
    K F Chung
    Section of Airways Disease, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, SW3 6LY, UK
    Eur Respir J 31:1334-56. 2008
    ..Treatments may be targeted to patients with specific mechanisms...
  43. ncbi request reprint Histone acetylation and deacetylation: importance in inflammatory lung diseases
    P J Barnes
    National Heart and Lung Institute, Imperial College, London SW3 6LY, UK
    Eur Respir J 25:552-63. 2005
    ..The reduction in histone deacetylase activity can be restored by theophylline, which may be able to reverse steroid resistance in chronic obstructive pulmonary disease and other inflammatory diseases...
  44. ncbi request reprint The effect of oxidative stress on histone acetylation and IL-8 release
    K Tomita
    Imperial College School of Science, Technology and Medicine, Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK
    Biochem Biophys Res Commun 301:572-7. 2003
    ..These data show that detection of acetylated histone residues at the single cell level using FACs may be a powerful new tool for the analysis of modulation of cell proliferation and gene transcription...
  45. ncbi request reprint Steroid resistance in severe asthma: current mechanisms and future treatment
    A Durham
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, UK
    Curr Pharm Des 17:674-84. 2011
    ....
  46. ncbi request reprint Glucocorticoid suppression of nuclear factor-kappa B: a role for histone modifications
    M Kagoshima
    Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK
    Biochem Soc Trans 31:60-5. 2003
    ..Understanding how corticosteroids work in asthma may help in designing novel corticosteroids with fewer systemic effects, as well as novel anti-inflammatory approaches...
  47. ncbi request reprint Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration
    K Ito
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK
    Biochem Biophys Res Commun 315:240-5. 2004
    ..This novel mechanism of inflammation may be important in increasing the severity and chronicity of inflammatory diseases...
  48. ncbi request reprint Glucocorticoid-mediated transrepression is regulated by histone acetylation and DNA methylation
    M Kagoshima
    Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK
    Eur J Pharmacol 429:327-34. 2001
    ..These data suggest that the mechanism of glucocorticoid action in suppressing interleukin-1 beta-stimulated GM-CSF release in A549 cells may involve modulation of CBP-mediated histone-acetylase activity and DNA methylation...
  49. ncbi request reprint How signaling pathways interact with gene transcription
    M Kagoshima
    Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY
    Monaldi Arch Chest Dis 59:30-7. 2003
    ....
  50. ncbi request reprint Molecular mechanisms of corticosteroid actions
    D N Payne
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6 LY, UK
    Paediatr Respir Rev 2:145-50. 2001
    ..This defect does not appear to be due to a reduced expression of GR but may be associated with a failure of GR to translocate into the nucleus and/or a reduced ability to inhibit AP-1 actions...
  51. ncbi request reprint Effect of dexamethasone on interleukin-1beta-(IL-1beta)-induced nuclear factor-kappaB (NF-kappaB) and kappaB-dependent transcription in epithelial cells
    R Newton
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK
    Eur J Biochem 254:81-9. 1998
    ....
  52. ncbi request reprint Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in children with difficult asthma, after treatment with oral prednisolone
    D N Payne
    Department of Paediatrics, Imperial College of Science, Technology and Medicine at the Royal Brompton Hospital and National Heart and Lung Institute, London, United Kingdom
    Am J Respir Crit Care Med 164:1376-81. 2001
    ..We propose that FE(NO) is associated with eosinophilic inflammation in children with difficult asthma, following prednisolone, and may help in identifying patients in whom persistent symptoms are associated with airway eosinophilia...
  53. ncbi request reprint Molecular mechanisms of corticosteroid actions
    I M Adcock
    Dept of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK
    Monaldi Arch Chest Dis 55:256-66. 2000
    ..Many of the detrimental side-effects of corticosteroids are believed to be due to gene induction, leading to the search for novel corticosteroids which can repress inflammatory genes without inducing gene transcription...
  54. pmc Suppression of lipopolysaccharide- and tumour necrosis factor-alpha-induced interleukin (IL)-8 expression by glucocorticoids involves changes in IL-8 promoter acetylation
    L G Tsaprouni
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
    Clin Exp Immunol 150:151-7. 2007
    ..Changes in histone acetylation at the IL-8 are important in its regulation by proinflammatory and anti-inflammatory agents, and modulation of this activity may have therapeutic potential in inflammatory conditions...
  55. ncbi request reprint Effects of dexamethasone on cytokine and phorbol ester stimulated c-Fos and c-Jun DNA binding and gene expression in human lung
    I M Adcock
    Dept of Thoracic Medicine, National Heart and Lung Institute, London, UK
    Eur Respir J 7:2117-23. 1994
    ..PMA induced a rapid and prolonged increase in c-Fos and c-Jun nuclear localization, which was not attenuated by co-incubation with dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)..
  56. pmc LPS induced inflammatory responses in human peripheral blood mononuclear cells is mediated through NOX4 and Gi╬▒ dependent PI-3kinase signalling
    Anta Ngkelo
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
    J Inflamm (Lond) 9:1. 2012
    ..This effect is apparently mediated through small G proteins facilitating the release of pro-inflammatory cytokines...
  57. ncbi request reprint Superinduction of COX-2 mRNA by cycloheximide and interleukin-1beta involves increased transcription and correlates with increased NF-kappaB and JNK activation
    R Newton
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK
    FEBS Lett 418:135-8. 1997
    ..These data are consistent with negative feed-back involving down-regulation of NF-kappaB by de novo IkappaB alpha synthesis and suggest that JNK activation may also be down-regulated by a cycloheximide sensitive process...
  58. ncbi request reprint Pathophysiological mechanisms of asthma. Application of cell and molecular biology techniques
    K F Chung
    National Heart and Lung Institute, Imperial College, Dovehouse St, London SW3 6LY, UK
    Mol Biotechnol 18:213-32. 2001
    ..The important outcome of this is that new preventive and curative treatments may ensue...
  59. ncbi request reprint Beta-adrenoceptor agonists interfere with glucocorticoid receptor DNA binding in rat lung
    M J Peters
    Department of Thoracic Medicine, National Heart and Lung Institute, London, UK
    Eur J Pharmacol 289:275-81. 1995
    ..We suggest that by this mechanism high doses of inhaled beta 2-adrenoceptor agonists may inhibit the anti-inflammatory effects of endogenous glucocorticoids and exogenous corticosteroids used for asthma therapy...
  60. pmc Chronic systemic administration of salmeterol to rats promotes pulmonary beta(2)-adrenoceptor desensitization and down-regulation of G(s alpha)
    P A Finney
    Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London
    Br J Pharmacol 132:1261-70. 2001
    ..The short-acting nature of salmeterol, when administered systemically, and the reduction in beta-adrenoceptor number may be due to metabolism to a biologically-active, short-acting and non-selective beta-adrenoceptor agonist...
  61. ncbi request reprint TGFbeta1 allele association with asthma severity
    L J Pulleyn
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse St, London SW3 6LY, UK
    Hum Genet 109:623-7. 2001
    ..In this study, we show that the -509T variant on haplotype 1 is the most informative marker of the TGFbeta1 contribution to asthma severity...
  62. ncbi request reprint Differential expression of IL-10 receptor by epithelial cells and alveolar macrophages
    S Lim
    Department of Thoracic Medicine, Imperial College School of Medicine, National Heart and Lung Institute, Dovehouse Street, London, UK
    Allergy 59:505-14. 2004
    ..Reduced IL-10 may result in exaggerated and more prolonged inflammatory responses in asthmatic airways. IL-10 acting through the IL-10 receptor (IL-10R) stimulates the transcription factors STAT1 and STAT3...
  63. ncbi request reprint Identification of the protein kinase C isoenzymes in human lung and airways smooth muscle at the protein and mRNA level
    B L Webb
    Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK
    Biochem Pharmacol 54:199-205. 1997
    ..Collectively, these data clearly demonstrate the expression of multiple PKC isoenzymes in human lung and tracheal smooth muscle, suggesting that they subserve diverse multifunctional roles in these tissues...
  64. ncbi request reprint Evidence for involvement of NF-kappaB in the transcriptional control of COX-2 gene expression by IL-1beta
    R Newton
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom
    Biochem Biophys Res Commun 237:28-32. 1997
    ..We conclude that IL-1beta stimulates PG production via transcriptional activation of COX-2 and provide evidence that this may involve NF-kappaB...
  65. ncbi request reprint Eotaxin: cloning of an eosinophil chemoattractant cytokine and increased mRNA expression in allergen-challenged guinea-pig lungs
    P J Jose
    Department of Applied Pharmacology, National Heart and Lung Institute, London, U K
    Biochem Biophys Res Commun 205:788-94. 1994
    ..As eotaxin stimulates human eosinophils, this chemokine and related molecules may be involved in human diseases such as asthma where eosinophil accumulation is a prominent feature...
  66. ncbi request reprint Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3
    Kittipong Maneechotesuwan
    Section of Airway Disease, National Heart and Lung Institute, Imperial College, London, United Kingdom
    J Immunol 178:2491-8. 2007
    ..This provides a means whereby allergen exposure leads to the expression of Th2 cytokines, and this novel mechanism may provide new approaches to treating allergic diseases...
  67. ncbi request reprint Role of TLR2, TLR4, and MyD88 in murine ozone-induced airway hyperresponsiveness and neutrophilia
    Alison 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...
  68. ncbi request reprint Attenuation of ozone-induced airway inflammation and hyper-responsiveness by c-Jun NH2 terminal kinase inhibitor SP600125
    Alison S Williams
    Airway Disease Section, National Heart and Lung Institute, Imperial College, Dovehouse St, London SW3 6LY, UK
    J Pharmacol Exp Ther 322:351-9. 2007
    ..Inhibition of JNK with small molecule kinase inhibitors may be a means of reducing ozone-induced inflammation and AHR...
  69. ncbi request reprint Oxidative stress and steroid resistance in asthma and COPD: pharmacological manipulation of HDAC-2 as a therapeutic strategy
    John A Marwick
    Novartis Institute for Biomedical Research, Respiratory Disease Area, Wimblehurst Road, Horsham, West Sussex, RH12 5AB, UK
    Expert Opin Ther Targets 11:745-55. 2007
    ..Once their mechanisms of action are established, it is likely that derivatives of these compounds may be used as a therapeutic strategy to restore corticosteroid insensitivity in the future...
  70. ncbi request reprint Corticosteroid inhibition of growth-related oncogene protein-alpha via mitogen-activated kinase phosphatase-1 in airway smooth muscle cells
    Razao Issa
    Experimental Medicine, Airway Studies Section, National Heart and Lung Institute, Imperial College, London, United Kingdom
    J Immunol 178:7366-75. 2007
    ..Glucocorticoids and IL-1beta or TNF-alpha modulate GRO-alpha release partly through the inhibition of JNK pathway, resulting from an up-regulation of MKP-1 expression...
  71. ncbi request reprint Overcoming steroid insensitivity in smoking asthmatics
    Tehireem Ahmad
    Imperial College London, National Heart and Lung Institute, Airways Disease Section, Dovehouse Street, London, SW3 6LY, UK
    Curr Opin Investig Drugs 9:470-7. 2008
    ..This review summarizes the various hypotheses underlying corticosteroid insensitivity in smoking asthmatics and discusses the development of potential novel therapies based on these concepts...
  72. ncbi request reprint Impact of protein acetylation in inflammatory lung diseases
    Kazuhiro Ito
    Airway Disease, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, United Kingdom
    Pharmacol Ther 116:249-65. 2007
    ..Further appreciation of the role of these changes may lead to the development of novel therapeutic approaches to inflammatory lung diseases that are currently difficult to treat...
  73. doi request reprint The role of histone deacetylases in asthma and allergic diseases
    Pankaj Bhavsar
    Cell and Molecular Biology, Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom
    J Allergy Clin Immunol 121:580-4. 2008
    ..Targeting specific enzymes involved in this process might lead to new therapeutic agents, particularly in situations in which current anti-inflammatory therapies are suboptimal...
  74. ncbi request reprint Attenuated production of intracellular IL-10 and IL-12 in monocytes from patients with severe asthma
    Katsuyuki Tomita
    Department of Thoracic Medicine, National Heart and Lung Institute at Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, United Kingdom
    Clin Immunol 102:258-66. 2002
    ..These results suggest that IL-10 synthesis is attenuated in severe persistent asthma compared to mild asthma and that this cannot be explained by the increase in the CD14(+)CD16(+) monocytes in asthma...
  75. ncbi request reprint p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma
    Elvis Irusen
    Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom
    J Allergy Clin Immunol 109:649-57. 2002
    ..IL-2 combined with IL-4 can alter glucocorticoid receptor (GR) ligand-binding affinity and modulate glucocorticoid function...
  76. ncbi request reprint Expression of nonmuscle cofilin-1 and steroid responsiveness in severe asthma
    Nisha Vasavda
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
    J Allergy Clin Immunol 118:1090-6. 2006
    ..Evidence in glucocorticoid-unresponsive Henrietta Lack (HeLa) cells indicated that cofilin-1 could act as an inhibitor of glucocorticoid function...
  77. ncbi request reprint Molecular interactions between glucocorticoids and long-acting beta2-agonists
    Ian M Adcock
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, UK
    J Allergy Clin Immunol 110:S261-8. 2002
    ....
  78. ncbi request reprint 5-Azacytidine suppresses RNA polymerase II recruitment to the SLPI gene
    Hiroo Wada
    Airway Disease Section, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
    Biochem Biophys Res Commun 331:93-9. 2005
    ....
  79. ncbi request reprint Triamcinolone acetonide and dexamethasome suppress TNF-alpha-induced histone H4 acetylation on lysine residues 8 and 12 in mononuclear cells
    Loukia G Tsaprouni
    Department of Biology Health Science, University of Luton, Luton LU1 3JU, UK
    Ann N Y Acad Sci 973:481-3. 2002
  80. ncbi request reprint Combination therapy of long-acting beta2-adrenoceptor agonists and corticosteroids for asthma
    K Fan Chung
    Imperial College, National Heart and Lung Institute, London, UK
    Treat Respir Med 3:279-89. 2004
    ..Improvements in combination therapy include a once-daily preparation and possible combination of inhaled corticosteroids with newer drugs such as phosphodiesterase IV inhibitors...
  81. ncbi request reprint Anti-inflammatory inhibitors of IkappaB kinase in asthma and COPD
    Gaetano Caramori
    Airways Disease Section, National Heart and Lung Institute, Imperal College London, Dovehouse Street, London SW3 6LY, UK
    Curr Opin Investig Drugs 5:1141-7. 2004
    ..Here, we review some of the major NFkappaB activating pathways, their role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD), and their potential as targets in the treatment of asthma and COPD...
  82. ncbi request reprint Effects of glucocorticoids on gene transcription
    Ryuji Hayashi
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse St, London, SW3 6LY, UK
    Eur J Pharmacol 500:51-62. 2004
    ..In addition, dissociated glucocorticoids that target NF-kappaB preferentially have also been successful in the treatment of allergic disease...
  83. ncbi request reprint Targeting Th2 cells in asthmatic airways
    Gaetano Caramori
    Dipartimento di Medicina Clinica e Sperimentale, Centro di Ricerca su Asma e BPCO, Universita di Ferrara, Italy
    Curr Drug Targets Inflamm Allergy 3:243-55. 2004
    ..Some of these new Th2-oriented strategies may in the future not only control symptoms, but also potentially prevent or cure the disease...
  84. pmc Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages
    Borja G Cosio
    Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse St, London SW3 6LY, England, UK
    J Exp Med 200:689-95. 2004
    ..Therefore, theophylline might restore steroid responsiveness in COPD patients...
  85. ncbi request reprint Defective glucocorticoid receptor nuclear translocation and altered histone acetylation patterns in glucocorticoid-resistant patients
    John G Matthews
    Thoracic Medicine, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Dovehouse Street, London SW3 6LY, United Kingdom
    J Allergy Clin Immunol 113:1100-8. 2004
    ..Most chronic inflammatory diseases are well controlled by glucocorticoids. However, a minority of patients fails to respond adequately to this treatment...
  86. pmc Effect of an inhibitor of Jun N-terminal protein kinase, SP600125, in single allergen challenge in sensitized rats
    Paul R Eynott
    Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK
    Immunology 112:446-53. 2004
    ..The role of JNK mitogen-activated protein kinase activation may be limited in the pathogenesis of bronchial hyperresponsiveness after single allergen exposure...
  87. ncbi request reprint Glucocorticoid receptor nitration leads to enhanced anti-inflammatory effects of novel steroid ligands
    Mark J Paul-Clark
    The William Harvey Research Institute, Queen Mary School of Medicine and Dentistry, London, United Kingdom
    J Immunol 171:3245-52. 2003
    ..In conclusion, we report here for the first time that posttranslational modification of GR by this novel nitrosteroid is associated with its enhanced anti-inflammatory activity...
  88. ncbi request reprint Histone acetylase and deacetylase activity in alveolar macrophages and blood mononocytes in asthma
    Borja G Cosio
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College Faculty of Medicine, London, United Kingdom
    Am J Respir Crit Care Med 170:141-7. 2004
    ..Glucocorticoids and theophylline may downregulate the inflammatory response by modulating HAT and HDAC activity, and nuclear factor-kappaB activation...
  89. ncbi request reprint Corticosteroid resistance in chronic obstructive pulmonary disease: inactivation of histone deacetylase
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK
    Lancet 363:731-3. 2004
    ..This hypothesis raises the possibility that novel therapeutic approaches might unlock this corticosteroid resistance, leading to more effective anti-inflammatory treatments for COPD and other severe inflammatory diseases...
  90. ncbi request reprint 13th European Respiratory Society Annual congress
    Loukia Tsaprouni
    Thoracic Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK
    Expert Opin Investig Drugs 12:1995-9. 2003
  91. ncbi request reprint Decreased histone deacetylase activity in chronic obstructive pulmonary disease
    Kazuhiro Ito
    Airway Disease Section, National Heart and Lung Institute, Imperial College, London, United Kingdom
    N Engl J Med 352:1967-76. 2005
    ..HDAC is a key molecule in the repression of production of proinflammatory cytokines in alveolar macrophages...
  92. ncbi request reprint Single-nucleotide polymorphisms associated with symptomatic infection and differential human gene expression in healthy seropositive persons each implicate the cytoskeleton, integrin signaling, and oncosuppression in the pathogenesis of human parvovirus B
    Jonathan R Kerr
    Department of Paediatric Infectious Diseases, St Mary s Campus, Imperial College, London, United Kingdom
    J Infect Dis 192:276-86. 2005
    ..Genes identified in both studies play a functional role in the cytoskeleton, integrin signaling, and oncosuppression, themes that have been shown to be important in parvovirus infections...
  93. ncbi request reprint Cigarette smoke activates human monocytes by an oxidant-AP-1 signaling pathway: implications for steroid resistance
    Matthew 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...
  94. ncbi request reprint IL-1 beta and TNF-alpha regulation of the adenosine receptor (A2A) expression: differential requirement for NF-kappa B binding to the proximal promoter
    Silvana Morello
    Airways Disease Section, NHLI Imperial College London, London, United Kingdom
    J Immunol 177:7173-83. 2006
    ....
  95. ncbi request reprint Therapeutic potential of phosphatidylinositol 3-kinase inhibitors in inflammatory respiratory disease
    Kazuhiro Ito
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, SW3, 6LY, UK
    J Pharmacol Exp Ther 321:1-8. 2007
    ..Encouraging data from animal models, primary cells and clinical studies in other diseases suggest that inhibitors of PI3K/Akt may prove to be useful novel therapies in the treatment of asthma and chronic obstructive pulmonary disease...
  96. pmc A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression
    Kazuhiro Ito
    Thoracic Medicine, Imperial College School of Science, Technology, and Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom
    Proc Natl Acad Sci U S A 99:8921-6. 2002
    ..Thus we have shown that low-dose theophylline exerts an anti-asthma effect through increasing activation of HDAC which is subsequently recruited by corticosteroids to suppress inflammatory genes...
  97. ncbi request reprint Molecular mechanisms of respiratory virus-induced asthma and COPD exacerbations and pneumonia
    Gaetano Caramori
    Centro di Ricerca su Asma e BPCO, University of Ferrara, Italy
    Curr Med Chem 13:2267-90. 2006
    ..Clearly this is an exciting new area of ongoing research with promising therapeutic potential...
  98. ncbi request reprint Divergent effect of mometasone on human eosinophil and neutrophil apoptosis
    Xianzhi Zhang
    The Immunopharmacological Research Group, Medical School, University of Tampere, FIN 33014 Tampere, Finland
    Life Sci 71:1523-34. 2002
    ..The present data suggests that mometasone has opposite effects on apoptosis of human eosinophils and neutrophils at clinically relevant drug concentrations via an effect on glucocorticoid receptor...
  99. ncbi request reprint Glucocorticoid receptor nuclear translocation in airway cells after inhaled combination therapy
    Omar S Usmani
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK
    Am J Respir Crit Care Med 172:704-12. 2005
    ..Together, our data confirm that GR nuclear translocation may underlie the complementary interactions between LABAs and corticosteroids, although the precise signal transduction mechanisms remain to be determined...
  100. ncbi request reprint Update on glucocorticoid action and resistance
    Kazuhiro Ito
    Cell and Molecular Biology, Airways Disease Section, National Heart and Lung Institute, Imperial College London, UK
    J Allergy Clin Immunol 117:522-43. 2006
    ....
  101. ncbi request reprint Expression and activity of histone deacetylases in human asthmatic airways
    Kazuhiro Ito
    Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London, SW3 6LY UK
    Am J Respir Crit Care Med 166:392-6. 2002
    ..The increase in HAT activity and reduced HDAC activity in asthma may underlie the increased expression of multiple inflammatory genes, and this is reversed, at least in part, by treatment with inhaled steroids...