Robert Newton

Summary

Affiliation: University of Calgary
Country: Canada

Publications

  1. doi request reprint Anti-inflammatory glucocorticoids: changing concepts
    Robert Newton
    Department of Cell Biology and Anatomy, Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1 Electronic address
    Eur J Pharmacol 724:231-6. 2014
  2. doi request reprint Pharmacological strategies for improving the efficacy and therapeutic ratio of glucocorticoids in inflammatory lung diseases
    Robert Newton
    Department of Cell Biology and Anatomy, Airway Inflammation Group, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    Pharmacol Ther 125:286-327. 2010
  3. ncbi request reprint Separating transrepression and transactivation: a distressing divorce for the glucocorticoid receptor?
    Robert Newton
    Department of Cell Biology and Anatomy, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada
    Mol Pharmacol 72:799-809. 2007
  4. doi request reprint Glucocorticoids inhibit IL-1beta-induced GM-CSF expression at multiple levels: roles for the ERK pathway and repression by MKP-1
    Robert Newton
    Airways Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N4N1
    Biochem J 427:113-24. 2010
  5. ncbi request reprint Repression of inflammatory gene expression in human pulmonary epithelial cells by small-molecule IkappaB kinase inhibitors
    Robert Newton
    Department of Cell Biology and Anatomy, Respiratory Research Group, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada
    J Pharmacol Exp Ther 321:734-42. 2007
  6. pmc Inhibition of NF-kappaB-dependent transcription by MKP-1: transcriptional repression by glucocorticoids occurring via p38 MAPK
    Elizabeth M King
    Airways Inflammation Group, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada
    J Biol Chem 284:26803-15. 2009
  7. pmc Glucocorticoid repression of inflammatory gene expression shows differential responsiveness by transactivation- and transrepression-dependent mechanisms
    Elizabeth M King
    Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    PLoS ONE 8:e53936. 2013
  8. pmc β2-Adrenoceptor agonist-induced RGS2 expression is a genomic mechanism of bronchoprotection that is enhanced by glucocorticoids
    Neil S Holden
    Airways Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, AB, Canada T2N 4N1
    Proc Natl Acad Sci U S A 108:19713-8. 2011
  9. doi request reprint Selective prostacyclin receptor agonism augments glucocorticoid-induced gene expression in human bronchial epithelial cells
    Sylvia M Wilson
    Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    J Immunol 183:6788-99. 2009
  10. doi request reprint Inflammatory stimuli inhibit glucocorticoid-dependent transactivation in human pulmonary epithelial cells: rescue by long-acting beta2-adrenoceptor agonists
    Christopher F Rider
    Airways Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    J Pharmacol Exp Ther 338:860-9. 2011

Collaborators

Detail Information

Publications55

  1. doi request reprint Anti-inflammatory glucocorticoids: changing concepts
    Robert Newton
    Department of Cell Biology and Anatomy, Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1 Electronic address
    Eur J Pharmacol 724:231-6. 2014
    ..This provides an explanation for glucocorticoid resistance. Continuing efforts to understand roles for glucocorticoid-dependent transactivation will provide opportunities to improve glucocorticoid therapies. ..
  2. doi request reprint Pharmacological strategies for improving the efficacy and therapeutic ratio of glucocorticoids in inflammatory lung diseases
    Robert Newton
    Department of Cell Biology and Anatomy, Airway Inflammation Group, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    Pharmacol Ther 125:286-327. 2010
    ..In this review, we discuss pharmacological methods by which selective GR modulators and "add-on" therapies may be exploited to improve the clinical efficacy of glucocorticoids while reducing potential adverse effects...
  3. ncbi request reprint Separating transrepression and transactivation: a distressing divorce for the glucocorticoid receptor?
    Robert Newton
    Department of Cell Biology and Anatomy, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada
    Mol Pharmacol 72:799-809. 2007
    ..Considerable care is therefore required to avoid loss of anti-inflammatory effectiveness in the development of novel transactivation-defective ligands of GR...
  4. doi request reprint Glucocorticoids inhibit IL-1beta-induced GM-CSF expression at multiple levels: roles for the ERK pathway and repression by MKP-1
    Robert Newton
    Airways Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N4N1
    Biochem J 427:113-24. 2010
    ..Thus de novo gene expression, particularly of MKP-1, is involved in the repressive effects of glucocorticoids...
  5. ncbi request reprint Repression of inflammatory gene expression in human pulmonary epithelial cells by small-molecule IkappaB kinase inhibitors
    Robert Newton
    Department of Cell Biology and Anatomy, Respiratory Research Group, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada
    J Pharmacol Exp Ther 321:734-42. 2007
    ....
  6. pmc Inhibition of NF-kappaB-dependent transcription by MKP-1: transcriptional repression by glucocorticoids occurring via p38 MAPK
    Elizabeth M King
    Airways Inflammation Group, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada
    J Biol Chem 284:26803-15. 2009
    ..We conclude that GR transactivation is essential to the anti-inflammatory properties of GR ligands...
  7. pmc Glucocorticoid repression of inflammatory gene expression shows differential responsiveness by transactivation- and transrepression-dependent mechanisms
    Elizabeth M King
    Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    PLoS ONE 8:e53936. 2013
    ..However, transactivation appears to account for the more potent and efficacious mechanism of repression by glucocorticoids on these IL-1β-induced genes...
  8. pmc β2-Adrenoceptor agonist-induced RGS2 expression is a genomic mechanism of bronchoprotection that is enhanced by glucocorticoids
    Neil S Holden
    Airways Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, AB, Canada T2N 4N1
    Proc Natl Acad Sci U S A 108:19713-8. 2011
    ....
  9. doi request reprint Selective prostacyclin receptor agonism augments glucocorticoid-induced gene expression in human bronchial epithelial cells
    Sylvia M Wilson
    Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    J Immunol 183:6788-99. 2009
    ..This observation may have clinical relevance in the treatment of airway inflammatory diseases that are either refractory or respond suboptimally to glucocorticoids...
  10. doi request reprint Inflammatory stimuli inhibit glucocorticoid-dependent transactivation in human pulmonary epithelial cells: rescue by long-acting beta2-adrenoceptor agonists
    Christopher F Rider
    Airways Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    J Pharmacol Exp Ther 338:860-9. 2011
    ....
  11. doi request reprint Induction of regulator of G-protein signaling 2 expression by long-acting β2-adrenoceptor agonists and glucocorticoids in human airway epithelial cells
    Neil S Holden
    Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada N S H, T G, C F R, A C, S S, M K, R L, M A G, R N GlaxoSmithKline Research and Development, Uxbridge, Middlesex, United Kingdom M J and Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, West Virginia D P S
    J Pharmacol Exp Ther 348:12-24. 2014
    ..Thus, RGS2 expression is a novel effector mechanism in the airway epithelium that is induced by glucocorticoid/LABA combinations. This could contribute to the efficacy of glucocorticoid/LABA combinations in asthma and COPD. ..
  12. doi request reprint Concurrent agonism of adenosine A2B and glucocorticoid receptors in human airway epithelial cells cooperatively induces genes with anti-inflammatory potential: a novel approach to treat chronic obstructive pulmonary disease
    Stephanie Greer
    Airways Inflammation Research Group, Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
    J Pharmacol Exp Ther 346:473-85. 2013
    ....
  13. doi request reprint Rhinovirus-induced MMP-9 expression is dependent on Fra-1, which is modulated by formoterol and dexamethasone
    Claire E Tacon
    Airway Inflammation Research Group, Snyder Institute for Chronic Diseases, Department of Medicine, University of Calgary, Calgary, Alberta T2N 4Z6, Canada
    J Immunol 188:4621-30. 2012
    ..Together, these results offer insights into the mechanisms by which long-acting β(2)-agonists and glucocorticoids might reduce HRV-related asthma exacerbations...
  14. doi request reprint Nitric oxide inhibits IFN regulatory factor 1 and nuclear factor-kappaB pathways in rhinovirus-infected epithelial cells
    Rommy Koetzler
    Airway Inflammation Group, Institute of Infection, Immunity and Inflammation, University of Calgary, Calgary, Alberta, Canada
    J Allergy Clin Immunol 124:551-7. 2009
    ....
  15. doi request reprint Regulation of tristetraprolin expression by interleukin-1 beta and dexamethasone in human pulmonary epithelial cells: roles for nuclear factor-kappa B and p38 mitogen-activated protein kinase
    Elizabeth M King
    Airways Inflammation Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    J Pharmacol Exp Ther 330:575-85. 2009
    ..Taken together, our data demonstrate that NF-kappaB and p38 MAPK are critical to the induction of TTP by IL-1beta and that TTP induction provides feedback control of the ARE-containing genes GM-CSF and IL-8...
  16. pmc Roles for the mitogen-activated protein kinase (MAPK) phosphatase, DUSP1, in feedback control of inflammatory gene expression and repression by dexamethasone
    Suharsh Shah
    From the Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta T2N 4Z6, Canada
    J Biol Chem 289:13667-79. 2014
    ..Therefore this also illustrates key roles for DUSP1-independent effectors in mediating glucocorticoid-dependent repression. ..
  17. doi request reprint Human rhinovirus infection up-regulates MMP-9 production in airway epithelial cells via NF-{kappa}B
    Claire E Tacon
    Department of Medicine, Snyder Institute of Infection, Immunity, and Inflammation, University of Calgary, Alberta, Canada
    Am J Respir Cell Mol Biol 43:201-9. 2010
    ..This increase in MMP-9 may be a mechanism by which rhinovirus infections contribute to airway inflammation and, potentially, to airway remodeling...
  18. doi request reprint Effect of beta2-adrenoceptor agonists and other cAMP-elevating agents on inflammatory gene expression in human ASM cells: a role for protein kinase A
    Manminder Kaur
    Dept of Cell Biology and Anatomy, Faculty of Medicine, Univ of Calgary, 3330 Hospital Dr NW, Calgary, AB, Canada T2N 4N1
    Am J Physiol Lung Cell Mol Physiol 295:L505-14. 2008
    ..Collectively, these results indicate that repression of IL-1beta-induced ICAM-1 expression and GM-CSF release by cAMP-elevating agents, including beta(2)-adrenoceptor agonists, may not occur through a generic effect on NF-kappaB...
  19. doi request reprint Modulation of transcriptional responses by poly(I:C) and human rhinovirus: effect of long-acting β₂-adrenoceptor agonists
    Christopher F Rider
    Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, Faculty of Medicine, University of Calgary, Calgary, 3330 Hospital Drive NW, AB, Canada T2N 4N1
    Eur J Pharmacol 708:60-7. 2013
    ....
  20. ncbi request reprint Analysis of the dissociated steroid RU24858 does not exclude a role for inducible genes in the anti-inflammatory actions of glucocorticoids
    Joanna E Chivers
    Department of Cell Biology and Anatomy, Respiratory Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    Mol Pharmacol 70:2084-95. 2006
    ..Thus, classic transactivation- and transrepressionbased screens for anti-inflammatory "dissociated" GR ligands may be flawed because they may not reflect the effects on real glucocorticoid-inducible genes...
  21. doi request reprint Human rhinovirus infection enhances airway epithelial cell production of growth factors involved in airway remodeling
    Richard Leigh
    Airway Inflammation Research Group, Department of Medicine, Institute of Infection, Immunity and Inflammation, University of Calgary, Calgary, Alberta, Canada
    J Allergy Clin Immunol 121:1238-1245.e4. 2008
    ..We reasoned that HRV infections might be important in the pathogenesis of airway remodeling, thereby providing a mechanism by which these children are at risk of asthma...
  22. doi request reprint Phosphodiesterase 4 inhibitors augment the ability of formoterol to enhance glucocorticoid-dependent gene transcription in human airway epithelial cells: a novel mechanism for the clinical efficacy of roflumilast in severe chronic obstructive pulmonary di
    Thunicia Moodley
    Department of Physiology and Pharmacology, University of Calgary, 3280 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1
    Mol Pharmacol 83:894-906. 2013
    ..Roflumilast may, therefore, be especially effective in patients with severe COPD...
  23. doi request reprint Evidence for a second receptor for prostacyclin on human airway epithelial cells that mediates inhibition of CXCL9 and CXCL10 release
    Sylvia M Wilson
    Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    Mol Pharmacol 79:586-95. 2011
    ..Collectively, these results indicate that PGI(2), taprostene and 15-deoxy-TIC suppress chemokine release from BEAS-2B cells by interacting with a novel IP receptor that we denote here as the "IP(2)" subtype...
  24. doi request reprint Phorbol ester-stimulated NF-kappaB-dependent transcription: roles for isoforms of novel protein kinase C
    Neil S Holden
    Airways Inflammation Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    Cell Signal 20:1338-48. 2008
    ....
  25. ncbi request reprint Long-acting beta2-adrenoceptor agonists synergistically enhance glucocorticoid-dependent transcription in human airway epithelial and smooth muscle cells
    Manminder Kaur
    Department of Cell Biology and Anatomy, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary T2N 4N1, Canada
    Mol Pharmacol 73:203-14. 2008
    ....
  26. pmc Cytokine-induced loss of glucocorticoid function: effect of kinase inhibitors, long-acting β(2)-adrenoceptor [corrected] agonist and glucocorticoid receptor ligands
    Christopher F Rider
    Airways Inflammation Research Group, Snyder Institute of Chronic Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    PLoS ONE 10:e0116773. 2015
    ..As similar effects were apparent on glucocorticoid-induced gene expression, the most effective strategy to overcome glucocorticoid resistance in this model was addition of formoterol to high efficacy NR3C1 agonists...
  27. doi request reprint How phosphodiesterase 4 inhibitors work in patients with chronic obstructive pulmonary disease of the severe, bronchitic, frequent exacerbator phenotype
    Mark A Giembycz
    Department of Physiology and Pharmacology, Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary, 3280 Hospital Drive Northwest, Calgary, Alberta T2N 4N1, Canada Electronic address
    Clin Chest Med 35:203-17. 2014
    ..The possibility that multivalent ligands may deliver superior efficacy is also being explored. Single molecules that inhibit PDE4 and activate β2-adrenoceptors at similar concentrations have been described. ..
  28. pmc Negative Feed-forward Control of Tumor Necrosis Factor (TNF) by Tristetraprolin (ZFP36) Is Limited by the Mitogen-activated Protein Kinase Phosphatase, Dual-specificity Phosphatase 1 (DUSP1): IMPLICATIONS FOR REGULATION BY GLUCOCORTICOIDS
    Suharsh Shah
    From the Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta T2N 4Z6, Canada
    J Biol Chem 291:110-25. 2016
    ..In summary, these data illustrate why understanding the competing effects of feedback and feed-forward control is relevant to the development of novel anti-inflammatory therapies. ..
  29. pmc DUSP1 Maintains IRF1 and Leads to Increased Expression of IRF1-dependent Genes: A MECHANISM PROMOTING GLUCOCORTICOID INSENSITIVITY
    Suharsh Shah
    From the Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada T2N 4Z6 and
    J Biol Chem 291:21802-21816. 2016
    ..Since IRF1-dependent genes, such as CXCL10, are central to host defense, these data may help explain the reduced effectiveness of glucocorticoids during asthma exacerbations...
  30. pmc Protective Roles for RGS2 in a Mouse Model of House Dust Mite-Induced Airway Inflammation
    Tresa George
    Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
    PLoS ONE 12:e0170269. 2017
    ..Modest anti-inflammatory and anti-remodelling roles for RGS2 are also suggested. If translatable to humans, therapies that maximize RGS2 expression may prove advantageous...
  31. doi request reprint Superiority of combined phosphodiesterase PDE3/PDE4 inhibition over PDE4 inhibition alone on glucocorticoid- and long-acting β2-adrenoceptor agonist-induced gene expression in human airway epithelial cells
    Hawazen BinMahfouz
    Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    Mol Pharmacol 87:64-76. 2015
    ..Collectively, these data provide a rationale for the use of PDE3 and PDE4 inhibitors in the treatment of COPD and asthma where they may enhance, sensitize, and prolong the effects of LABA/ICS combination therapies. ..
  32. doi request reprint Long-acting β2-agonists promote glucocorticoid-mediated repression of NF-κB by enhancing expression of the feedback regulator, TNFAIP3
    Mohammed Omar Altonsy
    University of Calgary, Airways Inflammation Research Group
    Am J Physiol Lung Cell Mol Physiol . 2016
    ..Repression of reporter activity by budesonide was increased by formoterol and involved TNFAIP3. Thus LABAs may improve the anti-inflammatory properties of ICSs by augmenting TNFAIP3 expression to negatively regulate NF-κB...
  33. pmc Understanding how long-acting β2 -adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids in asthma - an update
    Robert Newton
    Department of Cell Biology and Anatomy, Airways Inflammation Research Group, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
    Br J Pharmacol 173:3405-3430. 2016
    ..In all cases, the rational design of ICS/LABA, and derivative, combination therapies requires functional knowledge of induced (and repressed) genes for therapeutic benefit to be maximized...
  34. doi request reprint Harnessing the clinical efficacy of phosphodiesterase 4 inhibitors in inflammatory lung diseases: dual-selective phosphodiesterase inhibitors and novel combination therapies
    Mark A Giembycz
    Airways Inflammation Research Group, Departments of Physiology and Pharmacology, Institute of Infection, Immunity and Inflammation, University of Calgary, 3280 Hospital Drive NW, Calgary, AB T2N 4N1, Canada
    Handb Exp Pharmacol . 2011
    ....
  35. ncbi request reprint The role of IkappaB kinase 2, but not activation of NF-kappaB, in the release of CXCR3 ligands from IFN-gamma-stimulated human bronchial epithelial cells
    Susan J Tudhope
    Airway Disease, National Heart and Lung Institute, Imperial College, London, United Kingdom
    J Immunol 179:6237-45. 2007
    ..These data suggest that IKK2 is also involved in the IFN-gamma-stimulated release of the CXCR3 ligands through a novel mechanism that is independent NF-kappaB...
  36. ncbi request reprint Inhibitors of protein kinase C (PKC) prevent activated transcription: role of events downstream of NF-kappaB DNA binding
    Matthew C Catley
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, United Kingdom
    J Biol Chem 279:18457-66. 2004
    ....
  37. ncbi request reprint ICAM-1 expression is highly NF-kappaB-dependent in A549 cells. No role for ERK and p38 MAPK
    Neil S Holden
    Department of Biological Sciences, University of Warwick, Coventry, UK
    Eur J Biochem 271:785-91. 2004
    ..Taken together these data highlight the potential use of inhibition of the NF-kappaB signalling pathway in pulmonary inflammatory diseases and suggest that inhibitors of the p38 and ERK MAPK pathways may be of lesser effect...
  38. ncbi request reprint Cyclooxygenase-2 induction by bradykinin in human pulmonary artery smooth muscle cells is mediated by the cyclic AMP response element through a novel autocrine loop involving endogenous prostaglandin E2, E-prostanoid 2 (EP2), and EP4 receptors
    Dawn A Bradbury
    Division of Respiratory Medicine, University of Nottingham, City Hospital, Nottingham NG5 1PB, United Kingdom
    J Biol Chem 278:49954-64. 2003
    ..Collectively these studies indicate that COX-2 induction by BK in human pulmonary artery smooth muscle cells is mediated by the CRE through a novel autocrine loop involving endogenous PGE2...
  39. pmc Evidence for post-transcriptional regulation of interleukin-5 by dexamethasone
    Karl J Staples
    Department of Thoracic Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, UK
    Immunology 109:527-35. 2003
    ..Taken together, the results presented here suggest that, whilst transcriptional processes predominantly regulate IL-5 release, the mechanism by which dexamethasone inhibits IL-5 is post-transcriptional...
  40. ncbi request reprint Adenovirus-mediated delivery and expression of a cAMP-dependent protein kinase inhibitor gene to BEAS-2B epithelial cells abolishes the anti-inflammatory effects of rolipram, salbutamol, and prostaglandin E2: a comparison with H-89
    Koremu K Meja
    Thoracic Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
    J Pharmacol Exp Ther 309:833-44. 2004
    ..Furthermore, these data suggest that H-89 is not a selective inhibitor of PKA and should be avoided...
  41. pmc Nuclear factor-kappaB does not mediate the inhibitory effects of dexamethasone on granulocyte-macrophage colony-stimulating factor expression
    Martin W Bergmann
    Department of Thoracic Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK
    Immunology 111:430-4. 2004
    ..These data therefore confirm a critical role for both NF-kappaB and CLE0 sites in GM-CSF promoter activation and indicate that NF-kappaB may not mediate glucocorticoid-dependent repression of GM-CSF in these cells...
  42. ncbi request reprint Validation of the anti-inflammatory properties of small-molecule IkappaB Kinase (IKK)-2 inhibitors by comparison with adenoviral-mediated delivery of dominant-negative IKK1 and IKK2 in human airways smooth muscle
    Matthew C Catley
    National Heart and Lung Institute, Imperial College London, London, United Kingdom
    Mol Pharmacol 70:697-705. 2006
    ..We therefore suggest that IKK inhibitors may be of considerable benefit in inflammatory airways diseases, particularly in COPD or severe asthma, in which corticosteroids are ineffective...
  43. ncbi request reprint Ikappa-B kinase-2 inhibitor blocks inflammation in human airway smooth muscle and a rat model of asthma
    Mark A Birrell
    Respiratory Pharmacology Group, National Heart and Lung Institute, Imperial College Faculty of Medicine, London, UK
    Am J Respir Crit Care Med 172:962-71. 2005
    ..NF-kappaB is held inactive in the cytoplasm, bound to I-kappaB. The removal of I-kappaB, via the actions of inhibitor of kappaB (I-kappaB) kinase-2 (IKK-2), allows NF-kappaB to enter the nucleus...
  44. ncbi request reprint Differential effects of RU486 reveal distinct mechanisms for glucocorticoid repression of prostaglandin E release
    Joanna E Chivers
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, Faculty of Medicine, London, UK
    Eur J Biochem 271:4042-52. 2004
    ....
  45. pmc Validation of IKK beta as therapeutic target in airway inflammatory disease by adenoviral-mediated delivery of dominant-negative IKK beta to pulmonary epithelial cells
    Matthew C Catley
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Faculty of Medicine, London
    Br J Pharmacol 145:114-22. 2005
    ..Thus, novel therapies that target IKK beta could have potent anti-inflammatory effects and may be beneficial in the treatment of certain cancers...
  46. ncbi request reprint Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms
    Louise E Donnelly
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK
    Am J Physiol Lung Cell Mol Physiol 287:L774-83. 2004
    ..3 microM), and cyclooxygenase-2 expression in these cells. This study demonstrates that resveratrol and quercetin have novel nonsteroidal anti-inflammatory activity that may have applications for the treatment of inflammatory diseases...
  47. pmc Human transcriptome subtraction by using short sequence tags to search for tumor viruses in conjunctival carcinoma
    Huichen Feng
    Molecular Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
    J Virol 81:11332-40. 2007
    ..It provides, for the first time, quantitative evidence against some classes of viral etiology when no viral transcripts are found, thereby reducing the uncertainty involved in new pathogen discovery...
  48. ncbi request reprint Inhibitors of p38 mitogen-activated protein kinase: potential as anti-inflammatory agents in asthma?
    Robert Newton
    Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, UK
    BioDrugs 17:113-29. 2003
    ..However, these drugs may result in a complex phenotype that will require careful evaluation. Currently, a number of second or third generation inhibitors of p38 MAPK are being tested in phase I and phase II clinical trials...
  49. ncbi request reprint IL-1beta-dependent activation of NF-kappaB mediates PGE2 release via the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase
    Matthew C Catley
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College Faculty of Medicine, SW3 6LY, London, UK
    FEBS Lett 547:75-9. 2003
    ..However, other pathways are primarily responsible for PGE2 release induced by PMA...
  50. ncbi request reprint Regulation of kinin receptors in airway epithelial cells by inflammatory cytokines and dexamethasone
    Robert Newton
    Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London SW3, UK
    Eur J Pharmacol 441:193-202. 2002
    ..Arachidonic acid release in response to bradykinin was markedly enhanced by prior incubation with interleukin-1 beta and this was prevented by the prior addition of dexamethasone...
  51. ncbi request reprint Glucocorticoid inhibition of granulocyte macrophage-colony-stimulating factor from T cells is independent of control by nuclear factor-kappaB and conserved lymphokine element 0
    Martin W Bergmann
    Department of Thoracic Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom
    Am J Respir Cell Mol Biol 30:555-63. 2004
    ....
  52. ncbi request reprint Discovery of BRL 50481 [3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene], a selective inhibitor of phosphodiesterase 7: in vitro studies in human monocytes, lung macrophages, and CD8+ T-lymphocytes
    Susan J Smith
    Thoracic Medicine, National Heart and Lung Institute, Imperial College London, United Kingdom
    Mol Pharmacol 66:1679-89. 2004
    ..Furthermore, although BRL 50481 had only a modest inhibitory effect per se on the proinflammatory cells studied, it acted at least additively with other cAMP-elevating drugs, especially when HSPDE7A1 was up-regulated...
  53. ncbi request reprint Fractalkine/CX3CL1 production by human airway smooth muscle cells: induction by IFN-gamma and TNF-alpha and regulation by TGF-beta and corticosteroids
    Maria B Sukkar
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, Dovehouse St, SW3 6LY, London, UK
    Am J Physiol Lung Cell Mol Physiol 287:L1230-40. 2004
    ..In summary, FKN production by human ASMC in vitro is regulated by inflammatory and anti-inflammatory factors...
  54. ncbi request reprint Design and identification of selective HER-2 sheddase inhibitors via P1' manipulation and unconventional P2' perturbations to induce a molecular metamorphosis
    Wenqing Yao
    Incyte Corporation, Department of Medicinal Chemistry, Wilmington, DE 19880, USA
    Bioorg Med Chem Lett 18:159-63. 2008
    ..In addition, it was discovered that unconventional perturbation of the P2' moiety could confer MMP selectivity, which was hypothesized to be a manifestation of the P2' group effecting global conformational changes...
  55. pmc Identification in human airways smooth muscle cells of the prostanoid receptor and signalling pathway through which PGE2 inhibits the release of GM-CSF
    Deborah L Clarke
    Department of Thoracic Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, SW3 6LY
    Br J Pharmacol 141:1141-50. 2004
    ..In addition, the data illustrate that caution should be exercised when using H-89 in studies designed to assess the role of PKA in biological processes...