AJP - Lung AJP: Gastrointestinal and Liver Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 284: L548-L556, 2003. First published December 6, 2002; doi:10.1152/ajplung.00091.2002
1040-0605/03 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
284/3/L548    most recent
00091.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (26)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, G.
Right arrow Articles by Khalil, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, G.
Right arrow Articles by Khalil, N.
Vol. 284, Issue 3, L548-L556, March 2003

GM-CSF increases airway smooth muscle cell connective tissue expression by inducing TGF-beta receptors

Gang Chen1, Gary Grotendorst2, Thomas Eichholtz3, and Nasreen Khalil1

1 Department of Medicine, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver, British Columbia V6Z 3Z6, Canada; 2 University of Miami School of Medicine, Miami, Florida 33136; and 3 GlaxoSmithKline, Stevenage, Herts SG1 2NY, United Kingdom

Fibrosis around the smooth muscle of asthmatic airway walls leads to irreversible airway obstruction. Bronchial epithelial cells release granulocyte/macrophage colony-stimulating factor (GM-CSF) in asthmatics and are in close proximity to airway smooth muscle cells (ASMC). The findings in this study demonstrate that GM-CSF induces confluent, prolonged, serum-deprived cultures of ASMC to increase expression of collagen I and fibronectin. GM-CSF also induced ASMC to increase the expression of transforming growth factor (TGF)-beta receptors type I, II, and III (Tbeta R-I, Tbeta R-II, Tbeta R-III), but had no detectable effect on the release of TGF-beta 1 by the same ASMC. The presence of GM-CSF also induced the association of TGF-beta 1 with Tbeta R-III, which enhances binding of TGF-beta 1 to Tbeta R-II. The induction of Tbeta Rs was parallel to the increased induction of phosphorylated Smad2 (pSmad2) and connective tissue growth factor (CTGF), indicative of TGF-beta -mediated connective tissue synthesis. Dexamethasone decreased GM-CSF-induced Tbeta R-I, Tbeta R-II, Tbeta R-III, pSmad2, CTGF, collagen I, and fibronectin. In conclusion, GM-CSF increases the responsiveness of ASMC to TGF-beta 1-mediated connective tissue expression by induction of Tbeta Rs, which is inhibited by corticosteroids.

airway remodeling; corticosteroids; irreversible airway obstruction; phosphorylated Smad2; connective tissue growth factor; granulocyte/macrophage colony-stimulating factor; transforming growth factor-beta ; airway smooth muscle cells


This article has been cited by other articles:


Home page
 Eur Respir JHome page
J. E. Ward, T. Harris, T. Bamford, A. Mast, M. C. F. Pain, C. Robertson, D. Smallwood, T. Tran, J. Wilson, and A. G. Stewart
Proliferation is not increased in airway myofibroblasts isolated from asthmatics
Eur. Respir. J., August 1, 2008; 32(2): 362 - 371.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
J. Chhabra, Y-Z. Li, H. Alkhouri, A. E. Blake, Q. Ge, C. L. Armour, and J. M. Hughes
Histamine and tryptase modulate asthmatic airway smooth muscle GM-CSF and RANTES release
Eur. Respir. J., May 1, 2007; 29(5): 861 - 870.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
M. Ditiatkovski, B.-H. Toh, and A. Bobik
GM-CSF Deficiency Reduces Macrophage PPAR-{gamma} Expression and Aggravates Atherosclerosis in ApoE-Deficient Mice
Arterioscler Thromb Vasc Biol, October 1, 2006; 26(10): 2337 - 2344.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
M. E. Wylam, R. Ten, U. B. S. Prakash, H. F. Nadrous, M. L. Clawson, and P. M. Anderson
Aerosol granulocyte-macrophage colony-stimulating factor for pulmonary alveolar proteinosis.
Eur. Respir. J., March 1, 2006; 27(3): 585 - 593.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
W. Qi, S. Twigg, X. Chen, T. S. Polhill, P. Poronnik, R. E. Gilbert, and C. A. Pollock
Integrated actions of transforming growth factor-{beta}1 and connective tissue growth factor in renal fibrosis
Am J Physiol Renal Physiol, April 1, 2005; 288(4): F800 - F809.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
D. J. Lalor, B. Truong, S. Henness, A. E. Blake, Q. Ge, A. J. Ammit, C. L. Armour, and J. M. Hughes
Mechanisms of serum potentiation of GM-CSF production by human airway smooth muscle cells
Am J Physiol Lung Cell Mol Physiol, November 1, 2004; 287(5): L1007 - L1016.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
P.J. Barnes, S.D. Shapiro, and R.A. Pauwels
Chronic obstructive pulmonary disease: molecular and cellularmechanisms
Eur. Respir. J., October 1, 2003; 22(4): 672 - 688.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online