| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Antibody: Effect on the Smad Signaling Pathway1
* Leukocyte Biology Section, Division of Biomedical Sciences, Faculty of Medicine Imperial College, London, United Kingdom; and
Immunology and Transplantation Centre, Foundation of Biomedical Research of the Academy of Athens, Athens, Greece
Airway inflammation and remodeling are important pathophysiologic features of chronic asthma. Previously, we have developed a mouse model of prolonged allergen challenge which exhibits many characteristics of chronic asthma such as goblet cell hyperplasia and subepithelial collagen deposition, in association with an increase in lung expression of the profibrotic mediator, TGF-
. The aim of this study was to determine the effects of blockade of TGF- on the development of airway inflammation and remodeling using our murine model of prolonged allergen challenge. Importantly anti-TGF- Ab was administered therapeutically, with dosing starting after the onset of established eosinophilic airway inflammation. Therapeutic treatment of mice with anti-TGF- Ab significantly reduced peribronchiolar extracellular matrix deposition, airway smooth muscle cell proliferation, and mucus production in the lung without affecting established airway inflammation and Th2 cytokine production. Thus, our data suggest that it might be possible to uncouple airway inflammation and remodeling during prolonged allergen challenge. In addition, anti-TGF- Ab treatment was shown to regulate active TGF- signaling in situ with a reduction in the expression of phospho-Smad 2 and the concomitant up-regulation of Smad 7 in lung sections. Therefore, this is the first report to suggest that anti-TGF- Ab treatment prevents the progression of airway remodeling following allergen challenge even when given in a therapeutic mode. Moreover, the molecular mechanism behind this effect may involve regulation of active TGF- signaling.
This article has been cited by other articles:
|
|
 |
|
  H. Meurs, R. Gosens, and J. Zaagsma Airway hyperresponsiveness in asthma: lessons from in vitro model systems and animal models Eur. Respir. J., August 1, 2008; 32(2): 487 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Fattouh, N. G. Midence, K. Arias, J. R. Johnson, T. D. Walker, S. Goncharova, K. P. Souza, R. C. Gregory Jr., S. Lonning, J. Gauldie, et al. Transforming Growth Factor-{beta} Regulates House Dust Mite-induced Allergic Airway Inflammation but Not Airway Remodeling Am. J. Respir. Crit. Care Med., March 15, 2008; 177(6): 593 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Le Saux, K. Teeters, S. K. Miyasato, P. R. Hoffmann, O. Bollt, V. Douet, R. V. Shohet, D. H. Broide, and E. K. Tam Down-regulation of Caveolin-1, an Inhibitor of Transforming Growth Factor-{beta} Signaling, in Acute Allergen-induced Airway Remodeling J. Biol. Chem., February 29, 2008; 283(9): 5760 - 5768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Alcorn, L. M. Rinaldi, E. F. Jaffe, M. van Loon, J. H. T. Bates, Y. M. W. Janssen-Heininger, and C. G. Irvin Transforming Growth Factor-beta1 Suppresses Airway Hyperresponsiveness in Allergic Airway Disease Am. J. Respir. Crit. Care Med., November 15, 2007; 176(10): 974 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Xie, M. B. Sukkar, R. Issa, N. M. Khorasani, and K. F. Chung Mechanisms of induction of airway smooth muscle hyperplasia by transforming growth factor-beta Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L245 - L253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Le, J. Y. Cho, M. Miller, S. McElwain, K. Golgotiu, and D. H. Broide Inhibition of Allergen-Induced Airway Remodeling in Smad 3-Deficient Mice J. Immunol., June 1, 2007; 178(11): 7310 - 7316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sturrock, T. P. Huecksteadt, K. Norman, K. Sanders, T. M. Murphy, P. Chitano, K. Wilson, J. R. Hoidal, and T. P. Kennedy Nox4 mediates TGF-beta1-induced retinoblastoma protein phosphorylation, proliferation, and hypertrophy in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1543 - L1555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Lloyd and D. S. Robinson Allergen-induced airway remodelling Eur. Respir. J., May 1, 2007; 29(5): 1020 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Min, D. J. Song, M. Miller, J. Y. Cho, S. McElwain, P. Ferguson, and D. H. Broide Coexposure to Environmental Tobacco Smoke Increases Levels of Allergen-Induced Airway Remodeling in Mice J. Immunol., April 15, 2007; 178(8): 5321 - 5328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Torrego, M. Hew, T. Oates, M. Sukkar, and K. Fan Chung Expression and activation of TGF-{beta} isoforms in acute allergen-induced remodelling in asthma Thorax, April 1, 2007; 62(4): 307 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Fixman, A. Stewart, and J. G. Martin Basic mechanisms of development of airway structural changes in asthma Eur. Respir. J., February 1, 2007; 29(2): 379 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Maeda, V. Dave, and J. A. Whitsett Transcriptional Control of Lung Morphogenesis Physiol Rev, January 1, 2007; 87(1): 219 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Y. Leung, A. Niimi, A. Noble, T. Oates, A. S. Williams, S. Medicherla, A. A. Protter, and K. F. Chung Effect of Transforming Growth Factor-beta Receptor I Kinase Inhibitor 2,4-Disubstituted Pteridine (SD-208) in Chronic Allergic Airway Inflammation and Remodeling J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 586 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Bosse, C. Thompson, J. Stankova, and M. Rola-Pleszczynski Fibroblast Growth Factor 2 and Transforming Growth Factor beta1 Synergism in Human Bronchial Smooth Muscle Cell Proliferation Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 746 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Montagnoli, F. Fallarino, R. Gaziano, S. Bozza, S. Bellocchio, T. Zelante, W. P. Kurup, L. Pitzurra, P. Puccetti, and L. Romani Immunity and Tolerance to Aspergillus Involve Functionally Distinct Regulatory T Cells and Tryptophan Catabolism J. Immunol., February 1, 2006; 176(3): 1712 - 1723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Broide, T. Lawrence, T. Doherty, J. Y. Cho, M. Miller, K. McElwain, S. McElwain, and M. Karin Allergen-induced peribronchial fibrosis and mucus production mediated by I{kappa}B kinase {beta}-dependent genes in airway epithelium PNAS, December 6, 2005; 102(49): 17723 - 17728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Bronner Is the upregulation of bradykinin B2 receptors by TGF-{beta}1 one of the missing pieces in the "airway hyperresponsiveness" puzzle? Am J Physiol Lung Cell Mol Physiol, October 1, 2005; 289(4): L509 - L510. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
