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Am. J. Respir. Crit. Care Med., Volume 156, Number 2, August 1997, 591-599

Transforming Growth Factor-beta Expression in Mucosal Biopsies in Asthma and Chronic Bronchitis

ANTONIO M. VIGNOLA, PASCAL CHANEZ, GIUSEPPINA CHIAPPARA, ANNA MERENDINO, ELISABETTA PACE, AROLDO RIZZO, ANTONIO M. la ROCCA, VINCENZO BELLIA, GIOVANNI BONSIGNORE, and JEAN BOUSQUET

Clinique des Maladies Respiratoires and CJF 92-10 INSERM, Hôpital Arnaud de Villeneuve, 34295-Montpellier, France; Instituto di Fisiopatologia Respiratoria, C.N.R., Via Trabucco, Clinica di Malattie Respiratorie, Universita di Palermo, Servizio di Anatomia Patologica, Universita di Palermo, Palermo, Italy

We assessed whether transforming growth factor-beta (TGF-beta ), a fibrogenic growth factor, may be involved in remodeling of asthma and chronic bronchitis; its expression was compared with that of epidermal growth factor (EGF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in bronchial mucosal biopsies from 13 normal subjects, 24 asthmatics, and 19 patients with chronic bronchitis. TGF-beta immunoreactivity was highly increased in epithelium and submucosa of those with bronchitis and to a lesser extent in asthmatics. By comparison, with normal subjects, EGF immunoreactivity was significantly increased in the epithelium of bronchitic subjects and submucosa of asthmatics, and, GM-CSF immunoreactivity was increased in both epithelial and submucosal cells of asthmatics and to a lesser extent in submucosa of bronchitics. A significant correlation was found between the number of epithelial or submucosal cells expressing TGF-beta in both asthma and chronic bronchitis and basement membrane thickness and fibroblast number. No such correlation was found for EGF or GM-CSF. In situ hybridization for TGF-beta 1 mRNA confirmed the results obtained by immunohistochemistry. By combining in situ hybridization and immunohistochemistry, it was found that eosinophils and fibroblasts were synthetizing TGF-beta in asthma and bronchitis. These data suggest that TGF-beta , but not EGF or GM-CSF, is involved in airways remodeling in asthma and chronic bronchitis.




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Exacerbations and Progression of Disease in Asthma and Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, April 1, 2004; 1(2): 88 - 92.
[Abstract] [Full Text] [PDF]

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 Proc Am Thorac SocHome page
S. T. Holgate, J. Holloway, S. Wilson, F. Bucchieri, S. Puddicombe, and D. E. Davies
Epithelial-Mesenchymal Communication in the Pathogenesis of Chronic Asthma
Proceedings of the ATS, April 1, 2004; 1(2): 93 - 98.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
I Vachier, A M Vignola, G Chiappara, A Bruno, H Meziane, P Godard, J Bousquet, and P Chanez
Inflammatory features of nasal mucosa in smokers with and without COPD
Thorax, April 1, 2004; 59(4): 303 - 307.
[Abstract] [Full Text] [PDF]

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 ChestHome page
U. Bartram and C. P. Speer
The Role of Transforming Growth Factor {beta} in Lung Development and Disease
Chest, February 1, 2004; 125(2): 754 - 765.
[Abstract] [Full Text] [PDF]

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 BloodHome page
S. C. Pitchford, Y. Riffo-Vasquez, A. Sousa, S. Momi, P. Gresele, D. Spina, and C. P. Page
Platelets are necessary for airway wall remodeling in a murine model of chronic allergic inflammation
Blood, January 15, 2004; 103(2): 639 - 647.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
A. Barbato, G. Turato, S. Baraldo, E. Bazzan, F. Calabrese, M. Tura, R. Zuin, B. Beghe, P. Maestrelli, L. M. Fabbri, et al.
Airway Inflammation in Childhood Asthma
Am. J. Respir. Crit. Care Med., October 1, 2003; 168(7): 798 - 803.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
S.T. Holgate, D. E. Davies, S. Puddicombe, A. Richter, P. Lackie, J. Lordan, and P. Howarth
Mechanisms of airway epithelial damage: epithelial-mesenchymal interactions in the pathogenesis of asthma
Eur. Respir. J., September 20, 2003; 22(44_suppl): 24s - 29s.
[Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
K. Nagao, H. Tanaka, M. Komai, T. Masuda, S. Narumiya, and H. Nagai
Role of Prostaglandin I2 in Airway Remodeling Induced by Repeated Allergen Challenge in Mice
Am. J. Respir. Cell Mol. Biol., September 1, 2003; 29(3): 314 - 320.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
A. Dakhama, M. Kraft, R. J. Martin, and E. W. Gelfand
Induction of Regulated upon Activation, Normal T Cells Expressed and Secreted (RANTES) and Transforming Growth Factor-{beta}1 in Airway Epithelial Cells by Mycoplasma pneumoniae
Am. J. Respir. Cell Mol. Biol., September 1, 2003; 29(3): 344 - 351.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. J. Hodge, G. L. Hodge, P. N. Reynolds, R. Scicchitano, and M. Holmes
Increased production of TGF-{beta} and apoptosis of T lymphocytes isolated from peripheral blood in COPD
Am J Physiol Lung Cell Mol Physiol, August 1, 2003; 285(2): L492 - L499.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
M. P. O'Sullivan, J. W. Tyner, and M. J. Holtzman
Apoptosis in the Airways: Another Balancing Act in the Epithelial Program
Am. J. Respir. Cell Mol. Biol., July 1, 2003; 29(1): 3 - 7.
[Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
G. Pelaia, G. Cuda, A. Vatrella, D. Fratto, R. D. Grembiale, P. Tagliaferri, R. Maselli, F. S. Costanzo, and S. A. Marsico
Effects of Transforming Growth Factor-{beta} and Budesonide on Mitogen-Activated Protein Kinase Activation and Apoptosis in Airway Epithelial Cells
Am. J. Respir. Cell Mol. Biol., July 1, 2003; 29(1): 12 - 18.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
M. Schmidt, G. Sun, M. A. Stacey, L. Mori, and S. Mattoli
Identification of Circulating Fibrocytes as Precursors of Bronchial Myofibroblasts in Asthma
J. Immunol., July 1, 2003; 171(1): 380 - 389.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
M Profita, G Chiappara, F Mirabella, R Di Giorgi, L Chimenti, G Costanzo, L Riccobono, V Bellia, J Bousquet, and A M Vignola
Effect of cilomilast (Ariflo) on TNF-{alpha}, IL-8, and GM-CSF release by airway cells of patients with COPD
Thorax, July 1, 2003; 58(7): 573 - 579.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
T. Kobayashi, K. Iijima, and H. Kita
Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice
J. Immunol., June 1, 2003; 170(11): 5756 - 5763.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
L. Benayoun, A. Druilhe, M.-C. Dombret, M. Aubier, and M. Pretolani
Airway Structural Alterations Selectively Associated with Severe Asthma
Am. J. Respir. Crit. Care Med., May 15, 2003; 167(10): 1360 - 1368.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
G. Chen, G. Grotendorst, T. Eichholtz, and N. Khalil
GM-CSF increases airway smooth muscle cell connective tissue expression by inducing TGF-beta receptors
Am J Physiol Lung Cell Mol Physiol, March 1, 2003; 284(3): L548 - L556.
[Abstract] [Full Text] [PDF]

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 ChestHome page
A. M. Vignola, F. Mirabella, G. Costanzo, R. Di Giorgi, M. Gjomarkaj, V. Bellia, and G. Bonsignore
Airway Remodeling in Asthma
Chest, March 1, 2003; 123 (2009): 417S - 422S.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
D. J. Tschumperlin, J. D. Shively, T. Kikuchi, and J. M. Drazen
Mechanical Stress Triggers Selective Release of Fibrotic Mediators from Bronchial Epithelium
Am. J. Respir. Cell Mol. Biol., February 1, 2003; 28(2): 142 - 149.
[Abstract] [Full Text] [PDF]

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 FASEB J.Home page
S. KUNZMANN, J. G. WOHLFAHRT, S. ITOH, H. ASAO, M. KOMADA, C. A. AKDIS, K. BLASER, and C. B. SCHMIDT-WEBER
SARA and Hgs attenuate susceptibility to TGF-{beta}1-mediated T cell suppression
FASEB J, February 1, 2003; 17(2): 194 - 202.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
P A Beckett and P H Howarth
Pharmacotherapy and airway remodelling in asthma?
Thorax, February 1, 2003; 58(2): 163 - 174.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
C. Schramm, U. Herz, J. Podlech, M. Protschka, S. Finotto, M. J. Reddehase, H. Kohler, P. R. Galle, A. W. Lohse, and M. Blessing
TGF-{beta} Regulates Airway Responses Via T Cells
J. Immunol., February 1, 2003; 170(3): 1313 - 1319.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
J. K. Burgess, P. R. A. Johnson, Q. Ge, W. W. Au, M. H. Poniris, B. E. McParland, G. King, M. Roth, and J. L. Black
Expression of Connective Tissue Growth Factor in Asthmatic Airway Smooth Muscle Cells
Am. J. Respir. Crit. Care Med., January 1, 2003; 167(1): 71 - 77.
[Abstract] [Full Text] [PDF]

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 ChestHome page
M. J. Alvarez Puebla, R. Castillo, A. Rey, N. Ortega, C. Blanco, and T. Carrillo
Sputum Eosinophilia and Maximal Airway Narrowing in Dermatophagoides pteronyssinus Allergic Rhinitis Patients: Only Rhinitis or Rhinitis Plus Mild Asthma?
Chest, November 1, 2002; 122(5): 1560 - 1565.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
W. Ning, R. Song, C. Li, E. Park, A. Mohsenin, A. M. K. Choi, and M. E. Choi
TGF-beta 1 stimulates HO-1 via the p38 mitogen-activated protein kinase in A549 pulmonary epithelial cells
Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L1094 - L1102.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
E. Palmans, R.A. Pauwels, and J.C. Kips
Repeated allergen exposure changes collagen composition in airways of sensitised Brown Norway rats
Eur. Respir. J., August 1, 2002; 20(2): 280 - 285.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
F.-Q. Wen, T. Kohyama, X. Liu, Y. K. Zhu, H. Wang, H. J. Kim, T. Kobayashi, S. Abe, J. R. Spurzem, and S. I. Rennard
Interleukin-4- and Interleukin-13-Enhanced Transforming Growth Factor-beta 2 Production in Cultured Human Bronchial Epithelial Cells Is Attenuated by Interferon-gamma
Am. J. Respir. Cell Mol. Biol., April 1, 2002; 26(4): 484 - 490.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
M. T. Hopfenspirger and D. K. Agrawal
Airway Hyperresponsiveness, Late Allergic Response, and Eosinophilia Are Reversed with Mycobacterial Antigens in Ovalbumin-Presensitized Mice
J. Immunol., March 1, 2002; 168(5): 2516 - 2522.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
J. L. BLACK, M. ROTH, J. LEE, S. CARLIN, and P. R. A. JOHNSON
Mechanisms of Airway Remodeling . Airway Smooth Muscle
Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): S63 - 66.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
K.F. Chung
Cytokines in chronic obstructive pulmonary disease
Eur. Respir. J., July 2, 2001; 18(34_suppl): 50S - 59s.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
H. TAKIZAWA, M. TANAKA, K. TAKAMI, T. OHTOSHI, K. ITO, M. SATOH, Y. OKADA, F. YAMASAWA, K. NAKAHARA, and A. UMEDA
Increased Expression of Transforming Growth Factor-{beta}1 in Small Airway Epithelium from Tobacco Smokers and Patients with Chronic Obstructive Pulmonary Disease (COPD)
Am. J. Respir. Crit. Care Med., May 1, 2001; 163(6): 1476 - 1483.
[Abstract] [Full Text]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Coutts, G. Chen, N. Stephens, S. Hirst, D. Douglas, T. Eichholtz, and N. Khalil
Release of biologically active TGF-{beta} from airway smooth muscle cells induces autocrine synthesis of collagen
Am J Physiol Lung Cell Mol Physiol, May 1, 2001; 280(5): L999 - L1008.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
Y. Morishima, A. Nomura, Y. Uchida, Y. Noguchi, T. Sakamoto, Y. Ishii, Y. Goto, K. Masuyama, M. J. Zhang, K. Hirano, et al.
Triggering the Induction of Myofibroblast and Fibrogenesis by Airway Epithelial Shedding
Am. J. Respir. Cell Mol. Biol., January 1, 2001; 24(1): 1 - 11.
[Abstract] [Full Text]

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 Am. J. Respir. Crit. Care Med.Home page
P. R. A. JOHNSON, J. L. BLACK, S. CARLIN, Q. GE, and P. ANNE UNDERWOOD
The Production of Extracellular Matrix Proteins by Human Passively Sensitized Airway Smooth-Muscle Cells in Culture . The Effect of Beclomethasone
Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2145 - 2151.
[Abstract] [Full Text]

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 Am. J. Respir. Cell Mol. Bio.Home page
Y. Ohkawara, G. Tamura, T. Iwasaki, A. Tanaka, T. Kikuchi, and K. Shirato
Activation and Transforming Growth Factor-beta Production in Eosinophils by Hyaluronan
Am. J. Respir. Cell Mol. Biol., October 1, 2000; 23(4): 444 - 451.
[Abstract] [Full Text]

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 ThoraxHome page
A. M Vignola, R. Gagliardo, D. Guerrera, G. Chiappara, P. Chanez, J. Bousquet, and G. Bonsignore
New evidence of inflammation in asthma
Thorax, October 1, 2000; 55(90002): 59S - 60.
[Full Text]

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 FASEB J.Home page
S. M. PUDDICOMBE, R. POLOSA, A. RICHTER, M. T. KRISHNA, P. H. HOWARTH, S. T. HOLGATE, and D. E. DAVIES
Involvement of the epidermal growth factor receptor in epithelial repair in asthma
FASEB J, July 1, 2000; 14(10): 1362 - 1374.
[Abstract] [Full Text]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
B. Ressler, R. T. Lee, S. H. Randell, J. M. Drazen, and R. D. Kamm
Molecular responses of rat tracheal epithelial cells to transmembrane pressure
Am J Physiol Lung Cell Mol Physiol, June 1, 2000; 278(6): L1264 - L1272.
[Abstract] [Full Text] [PDF]


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