Am. J. Respir. Cell Mol. Biol., Vol 17, No. 3, Sep 1997, 326-333.
Eosinophil-associated TGF-beta1 mRNA expression and airways fibrosis in bronchial asthma
EM Minshall, DY Leung, RJ Martin, YL Song, L Cameron, P Ernst and Q Hamid
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
The histopathology of bronchial asthma is associated with structural
changes within the airways, including subepithelial fibrosis, as well as
chronic eosinophilic inflammation. The mechanisms responsible for this
tissue remodeling, and in particular the role of inflammatory cells, remain
to be established. Transforming growth factor-beta (TGF- beta) is a potent
profibrotic cytokine which may contribute to the thickening of the
reticular lamina by the deposition of collagen fibers. To investigate the
molecular mechanisms underlying these structural changes, we have
investigated the expression of TGF-beta1 mRNA and immunoreactivity within
the bronchial mucosa of mild to severe asthmatic individuals and normal
control subjects using the techniques of in situ hybridization and
immunocytochemistry. As eosinophils are prominent within the asthmatic
airway and are known to synthesize pro- inflammatory cytokines, the
presence of TGF-beta1 mRNA and immunoreactive protein in eosinophils was
also examined. Asthmatic individuals exhibited a greater expression of
TGF-beta1 mRNA and immunoreactivity in the airways submucosa than normal
control subjects (P < 0.05), and these increases were directly related
to the severity of the disorder. The extent of airways fibrosis, as
detected histochemically, was also increased in asthmatics compared with
normal control subjects (P < 0.005). In asthmatic subjects, the presence
of subepithelial fibrosis was associated with the severity of the disease
and correlated with the decline in forced expiratory volume in 1 s (r2 =
0.78; P < 0.05). Within the asthmatic airways, EG2-positive eosinophils
represented the major source of TGF-beta1 mRNA and immunoreactivity. These
results provide evidence that TGF-beta1 may play a role in the fibrotic
changes occurring within asthmatic airways and that activated eosinophils
are a major source of this cytokine.
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C. G. Lee, S. J. Cho, M. J. Kang, S. P. Chapoval, P. J. Lee, P. W. Noble, T. Yehualaeshet, B. Lu, R. A. Flavell, J. Milbrandt, et al.
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H. Tanaka, M. Komai, K. Nagao, M. Ishizaki, D. Kajiwara, K. Takatsu, G. Delespesse, and H. Nagai
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U. Bartram and C. P. Speer
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E. S. Silverman, L. J. Palmer, V. Subramaniam, A. Hallock, S. Mathew, J. Vallone, D. S. Faffe, T. Shikanai, B. A. Raby, S. T. Weiss, et al.
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S. C. Pitchford, Y. Riffo-Vasquez, A. Sousa, S. Momi, P. Gresele, D. Spina, and C. P. Page
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A. Barbato, G. Turato, S. Baraldo, E. Bazzan, F. Calabrese, M. Tura, R. Zuin, B. Beghe, P. Maestrelli, L. M. Fabbri, et al.
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P. Jeffery, S. Holgate, and S. Wenzel
Methods for the Assessment of Endobronchial Biopsies in Clinical Research: Application to Studies of Pathogenesis and the Effects of Treatment
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N J Kenyon, R W Ward, G McGrew, and J A Last
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K. Nagao, H. Tanaka, M. Komai, T. Masuda, S. Narumiya, and H. Nagai
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A. Dakhama, M. Kraft, R. J. Martin, and E. W. Gelfand
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M. P. O'Sullivan, J. W. Tyner, and M. J. Holtzman
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L. Benayoun, A. Druilhe, M.-C. Dombret, M. Aubier, and M. Pretolani
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P A Beckett and P H Howarth
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C. Schramm, U. Herz, J. Podlech, M. Protschka, S. Finotto, M. J. Reddehase, H. Kohler, P. R. Galle, A. W. Lohse, and M. Blessing
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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
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S. H. P. Oliveira, D. D. Taub, J. Nagel, R. Smith, C. M. Hogaboam, A. Berlin, and N. W. Lukacs
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M. J. Alvarez Puebla, R. Castillo, A. Rey, N. Ortega, C. Blanco, and T. Carrillo
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J. D. Savov, S. H. Gavett, D. M. Brass, D. L. Costa, and D. A. Schwartz
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S. Phipps, S. Ying, A. Wangoo, Y.-E. Ong, F. Levi-Schaffer, and A. B. Kay
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S. E. Wenzel, J. B. Trudeau, S. Barnes, X. Zhou, M. Cundall, J. Y. Westcott, K. McCord, and H. W. Chu
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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
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M. T. Hopfenspirger and D. K. Agrawal
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A. T. HASTIE, W. K. KRAFT, K. B. NYCE, J. G. ZANGRILLI, A. I. MUSANI, J. E. FISH, and S. P. PETERS
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A. Kamachi, Y. Nasuhara, M. Nishimura, T. Takahashi, Y. Homma, Y. Ohtsuka, and M. Munakata
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P. K. JEFFERY
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A. ten BRINKE, A. H. ZWINDERMAN, P. J. STERK, K. F. RABE, and E. H. BEL
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P.J. Barnes
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S. M. Ensminger, B. M. Spriewald, H. V. Sorensen, O. Witzke, E. G. Flashman, A. Bushell, P. J. Morris, M. L. Rose, A. Rahemtulla, and K. J. Wood
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A. Coutts, G. Chen, N. Stephens, S. Hirst, D. Douglas, T. Eichholtz, and N. Khalil
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J.C. Kips, K.G. Tournoy, and R.A. Pauwels
New anti-asthma therapies: suppression of the effect of interleukin (IL)-4 and IL-5
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C. L. S. George, H. Jin, C. L. Wohlford-Lenane, M. E. O'Neill, J. C. Phipps, P. O'Shaughnessy, J. N. Kline, P. S. Thorne, and D. A. Schwartz
Endotoxin responsiveness and subchronic grain dust-induced airway disease
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S. Wenzel
Proceedings of the ATS Workshop on Refractory Asthma . Current Understanding, Recommendations, and Unanswered Questions
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J. Wang, R. J. Homer, Q. Chen, and J. A. Elias
Endogenous and Exogenous IL-6 Inhibit Aeroallergen-Induced Th2 Inflammation
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S. T. HOLGATE, P. LACKIE, S. WILSON, W. ROCHE, and D. DAVIES
Bronchial Epithelium as a Key Regulator of Airway Allergen Sensitization and Remodeling in Asthma
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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
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S. Ali, J. Kaur, and K. D. Patel
Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and Regulated on Activation Normal T Cell Expressed and Secreted Are Expressed by Human Breast Carcinoma Cells and Support Eosinophil Adhesion and Activation
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R. O. Sanchez Mejia, B. K. Lam, and J. P. Arm
Matrix-Associated Transforming Growth Factor-beta 1 Primes Mouse Bone Marrow-Derived Mast Cells for Increased High-Affinity Fc Receptor for Immunoglobulin E-Dependent Eicosanoid Biosynthesis
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J. BOUSQUET, P. K. JEFFERY, W. W. BUSSE, M. JOHNSON, and A. M. VIGNOLA
Asthma . From Bronchoconstriction to Airways Inflammation and Remodeling
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A. Oriente, N. S. Fedarko, S. E. Pacocha, S.-K. Huang, L. M. Lichtenstein, and D. M. Essayan
Interleukin-13 Modulates Collagen Homeostasis in Human Skin and Keloid Fibroblasts
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P. Cohen, R. Rajah, J. Rosenbloom, and D. J. Herrick
IGFBP-3 mediates TGF-beta 1-induced cell growth in human airway smooth muscle cells
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K. Sato, H. Kawasaki, H. Nagayama, M. Enomoto, C. Morimoto, K. Tadokoro, T. Juji, and T. A. Takahashi
TGF-{beta}1 Reciprocally Controls Chemotaxis of Human Peripheral Blood Monocyte-Derived Dendritic Cells Via Chemokine Receptors
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Copyright © 1997 American Thoracic Society.
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