help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Tschumperlin, D. J.
Right arrow Articles by Drazen, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tschumperlin, D. J.
Right arrow Articles by Drazen, J. M.
American Journal of Respiratory Cell and Molecular Biology. Vol. 28, pp. 142-149, 2003
© 2003 American Thoracic Society
DOI: 10.1165/rcmb.2002-0121OC

Mechanical Stress Triggers Selective Release of Fibrotic Mediators from Bronchial Epithelium

Daniel J. Tschumperlin, Jonathan D. Shively, Tadashi Kikuchi and Jeffrey M. Drazen

Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; and Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts

Address correspondence to: Jeffrey M. Drazen, Pulmonary and Critical Care Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. E-mail: jdrazen{at}nejm.org

Transforming growth factor-ß (TGF-ß) and endothelin (ET) are found in elevated amounts in the airways of individuals with asthma. The cellular source of these peptides and their role in mediating the airway fibrosis of chronic asthma are unknown. In response to mechanical stresses similar to those occurring in vivo during airway constriction, bronchial epithelial cells increase the steady-state level of mRNA for both ET-1 and ET-2, followed by increased release of ET protein. Mechanical stress also enhances release of TGF-ß2 from a preformed cell-associated pool. TGF-ß2 and ET act individually and, more importantly, synergistically to promote fibrotic protein synthesis in reporter fibroblasts. To confirm the role of these intermediates in stress-induced fibrosis, conditioned medium from mechanically stressed bronchial epithelial cells was shown to elicit fibrotic protein synthesis in reporter fibroblasts; this effect was significantly inhibited by combined treatment with ET receptor antagonists and a neutralizing antibody to TGF-ß2. These data are consistent with a primary pathogenic role for mechanical stress–induced release of both TGF-ß2 and ET in the subepithelial fibrosis that characterizes chronic asthma.

Abbreviations: bronchial epithelial basal media supplemented with growth factors, BEGM • Dulbecco's modified Eagle's medium, DMEM • enzyme-linked immunosorbent assay, ELISA • endothelin, ET • normal human bronchial epithelial, NHBE • phosphate-buffered saline, PBS • platelet-derived growth factor, PDGF • reverse transcriptase–polymerase chain reaction, RT-PCR • trichloroacetic acid, TCA • transforming growth factor, TGF




This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
T. Khan, E. S. Muise, P. Iyengar, Z. V. Wang, M. Chandalia, N. Abate, B. B. Zhang, P. Bonaldo, S. Chua, and P. E. Scherer
Metabolic Dysregulation and Adipose Tissue Fibrosis: Role of Collagen VI
Mol. Cell. Biol., March 15, 2009; 29(6): 1575 - 1591.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. A. Tomei, M. M. Choe, and M. A. Swartz
Effects of dynamic compression on lentiviral transduction in an in vitro airway wall model
Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L79 - L86.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
L. Y. Leung, D. Tian, C. P. Brangwynne, D. A. Weitz, and D. J. Tschumperlin
A new microrheometric approach reveals individual and cooperative roles for TGF-{beta}1 and IL-1{beta} in fibroblast-mediated stiffening of collagen gels
FASEB J, July 1, 2007; 21(9): 2064 - 2073.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. McWhinnie, D. V. Pechkovsky, D. Zhou, D. Lane, A. J. Halayko, D. A. Knight, and T. R. Bai
Endothelin-1 induces hypertrophy and inhibits apoptosis in human airway smooth muscle cells
Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L278 - L286.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
E. K. Chu, J. Cheng, J. S. Foley, B. H. Mecham, C. A. Owen, K. J. Haley, T. J. Mariani, I. S. Kohane, D. J. Tschumperlin, and J. M. Drazen
Induction of the Plasminogen Activator System by Mechanical Stimulation of Human Bronchial Epithelial Cells
Am. J. Respir. Cell Mol. Biol., December 1, 2006; 35(6): 628 - 638.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
H. G. R. Thompson, J. D. Mih, T. B. Krasieva, B. J. Tromberg, and S. C. George
Epithelial-derived TGF-beta2 modulates basal and wound-healing subepithelial matrix homeostasis
Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1277 - L1285.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. M. Choe, P. H. S. Sporn, and M. A. Swartz
Extracellular Matrix Remodeling by Dynamic Strain in a Three-Dimensional Tissue-Engineered Human Airway Wall Model
Am. J. Respir. Cell Mol. Biol., September 1, 2006; 35(3): 306 - 313.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
X. Trepat, F. Puig, N. Gavara, J. J. Fredberg, R. Farre, and D. Navajas
Effect of stretch on structural integrity and micromechanics of human alveolar epithelial cell monolayers exposed to thrombin
Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1104 - L1110.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
C. Bergeron and L.-P. Boulet
Structural changes in airway diseases: characteristics, mechanisms, consequences, and pharmacologic modulation.
Chest, April 1, 2006; 129(4): 1068 - 1087.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
E. K. Chu and J. M. Drazen
Asthma: One Hundred Years of Treatment and Onward
Am. J. Respir. Crit. Care Med., June 1, 2005; 171(11): 1202 - 1208.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
R. S. Tepper, R. Ramchandani, E. Argay, L. Zhang, Z. Xue, Y. Liu, and S. J. Gunst
Chronic strain alters the passive and contractile properties of rabbit airways
J Appl Physiol, May 1, 2005; 98(5): 1949 - 1954.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
I A Fedorov, S J Wilson, D E Davies, and S T Holgate
Epithelial stress and structural remodelling in childhood asthma
Thorax, May 1, 2005; 60(5): 389 - 394.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. Fukunaga, P. Kohli, C. Bonnans, L. E. Fredenburgh, and B. D. Levy
Cyclooxygenase 2 Plays a Pivotal Role in the Resolution of Acute Lung Injury
J. Immunol., April 15, 2005; 174(8): 5033 - 5039.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
H. W. Chu, S. Balzar, G. J. Seedorf, J. Y. Westcott, J. B. Trudeau, P. Silkoff, and S. E. Wenzel
Transforming Growth Factor-{beta}2 Induces Bronchial Epithelial Mucin Expression in Asthma
Am. J. Pathol., October 1, 2004; 165(4): 1097 - 1106.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. A. Olman
Epithelial Cell Modulation of Airway Fibrosis in Asthma
Am. J. Respir. Cell Mol. Biol., February 1, 2003; 28(2): 125 - 128.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2003 American Thoracic Society. 		  CCM abstracts