help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

Published ahead of print on August 29, 2007, doi:10.1164/rccm.200702-334OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Online Supplement
Right arrow All Versions of this Article:
200702-334OCv1
176/10/974    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Alcorn, J. F.
Right arrow Articles by Irvin, C. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alcorn, J. F.
Right arrow Articles by Irvin, C. G.
American Journal of Respiratory and Critical Care Medicine Vol 176. pp. 974-982, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200702-334OC


Original Article

Transforming Growth Factor-beta1 Suppresses Airway Hyperresponsiveness in Allergic Airway Disease

John F. Alcorn1, Lisa M. Rinaldi2, Elizabeth F. Jaffe2, Mirjam van Loon2, Jason H. T. Bates2, Yvonne M. W. Janssen-Heininger1 and Charles G. Irvin2

1 Department of Pathology and 2 Department of Medicine, University of Vermont, Burlington, Vermont

Correspondence and requests for reprints should be addressed to John F. Alcorn, Ph.D., 223 HSRF, Department of Pathology, University of Vermont, Burlington, VT 05405. E-mail: john.alcorn{at}med.uvm.edu

Rationale: Asthma is characterized by increases in airway resistance, pulmonary remodeling, and lung inflammation. The cytokine transforming growth factor (TGF)-beta has been shown to have a central role in asthma pathogenesis and in mouse models of allergic airway disease.

Objectives: To determine the contribution of TGF-beta to airway hyperresponsiveness (AHR), we examined the time course, source, and isoform specificity of TGF-beta production in an in vivo mouse asthma model. To then elucidate the function of TGF-beta in AHR, inflammation, and pulmonary fibrosis, we examined the effects of blocking TGF-beta signaling with neutralizing antibody.

Methods: Mice were sensitized and challenged with ovalbumin (OVA) to establish allergic airway disease. TGF-beta activity was neutralized by intranasal administration of monoclonal antibody.

Measurements and Main Results: TGF-beta1 protein levels were increased in OVA-challenged lungs versus naive controls, and airway epithelial cells were shown to be a likely source of TGF-beta1. In addition, TGF-beta1 levels were elevated in OVA-exposed IL-5–null mice, which fail to recruit eosinophils into the airways. Neutralization of TGF-beta1 with specific antibody had no significant effect on airway inflammation and eosinophilia, although anti–TGF-beta1 antibody enhanced OVA-induced AHR and suppressed pulmonary fibrosis.

Conclusions: These data show that TGF-beta1 is the main TGF-beta isoform produced after OVA challenge, with a likely cellular source being the airway epithelium. The effects of blocking TGF-beta1 signaling had differential effects on AHR, fibrosis, and inflammation. While TGF-beta neutralization may be beneficial to abrogating airway remodeling, it may be detrimental to lung function by increasing AHR.

Key Words: lung • mice • hypersensitivity • cytokines


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Transforming growth factor (TGF)-beta1 is known to play a critical role in promoting pulmonary remodeling; however, its contribution to airway hyperresponsiveness (AHR) is less well defined.

What This Study Adds to the Field
TGF-beta1 is the predominant TGF-beta isoform produced in a mouse asthma model and neutralization of TGF-beta1 results in less fibrosis and increased AHR.

 



This article has been cited by other articles:


Home page
Am. J. Respir. Crit. Care Med.Home page
W. C. Moore
Update in Asthma 2007
Am. J. Respir. Crit. Care Med., May 15, 2008; 177(10): 1068 - 1073.
[Full Text] [PDF]


Home page
J. Immunol.Home page
Y. A. Taher, B. C. A. M. van Esch, G. A. Hofman, P. A. J. Henricks, and A. J. M. van Oosterhout
1{alpha},25-Dihydroxyvitamin D3 Potentiates the Beneficial Effects of Allergen Immunotherapy in a Mouse Model of Allergic Asthma: Role for IL-10 and TGF-{beta}
J. Immunol., April 15, 2008; 180(8): 5211 - 5221.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Crit. Care Med.Home page
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]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2007 American Thoracic Society