Am. J. Respir. Crit. Care Med., Volume 156, Number 2, August 1997, 642-647

Transforming Growth Factor-1 in Asthma
Measurement in Bronchoalveolar Lavage Fluid

ANTHONY E. REDINGTON, JACQUELINE MADDEN, ANTHONY J. FREW, RATKO DJUKANOVIC, WILLIAM R. ROCHE, STEPHEN T. HOLGATE, and PETER H. HOWARTH

University Medicine and University Pathology, Southampton General Hospital, Southampton, United Kingdom

Airway wall remodeling is an established pathological feature in asthma. Its causes are not well understood, but one mediator of potential relevance is transforming growth factor-beta 1 (TGF-1). We have measured levels of immunoreactive TGF-1 in bronchoalveolar lavage (BAL) fluid from clinically stable atopic asthmatics and healthy control subjects. We have also examined the influence of allergen exposure on TGF-1 release in the airways using a segmental bronchoprovocation model, with BAL performed at two time points following endobronchial allergen and sham saline challenges. Basal concentrations of TGF-1 were significantly higher in asthmatics than control subjects (median 8.0 versus 5.5 pg/ml, p = 0.027). Following segmental bronchoprovocation, concentrations of TGF- 1 at the allergen- and saline-challenged sites were not significantly different after 10 min, (31.3 versus 25.0 pg/ml, p = 0.78), but after 24 h there were significantly higher TGF-1 concentrations at the allergen-challenged sites (46.0 versus 21.5 pg/ml, p = 0.017). We conclude that basal TGF-1 levels in the airways are elevated in atopic asthma and that these levels increase further in response to allergen exposure. These findings are consistent with the hypothesis that TGF-1 is implicated in airway wall remodeling in asthma.

This article has been cited by other articles:

				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]

				D. M. Murphy, I. A. Forrest, P. A. Corris, G. E. Johnson, T. Small, D. Jones, A. J. Fisher, J. J. Egan, T. E. Cawston, C. Ward, et al. Simvastatin attenuates release of neutrophilic and remodeling factors from primary bronchial epithelial cells derived from stable lung transplant recipients Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L592 - L599. [Abstract] [Full Text] [PDF]

				C. J. Le Saux, K. Teeters, S. K. Miyasato, P. R. Hoffmann, O. Bollt, V. Douet, R. V. Shohet, D. H. Broide, and E. K. Tam Down-regulation of Caveolin-1, an Inhibitor of Transforming Growth Factor-{beta} Signaling, in Acute Allergen-induced Airway Remodeling J. Biol. Chem., February 29, 2008; 283(9): 5760 - 5768. [Abstract] [Full Text] [PDF]

				A. Semlali, E. Jacques, S. Plante, S. Biardel, J. Milot, M. Laviolette, L.-P. Boulet, and J. Chakir TGF- Suppresses EGF-Induced MAPK Signaling and Proliferation in Asthmatic Epithelial Cells Am. J. Respir. Cell Mol. Biol., February 1, 2008; 38(2): 202 - 208. [Abstract] [Full Text] [PDF]

				M. T. Salam, W. J. Gauderman, R. McConnell, P.-C. Lin, and F. D. Gilliland Transforming Growth Factor- 1 C-509T Polymorphism, Oxidant Stress, and Early-Onset Childhood Asthma Am. J. Respir. Crit. Care Med., December 15, 2007; 176(12): 1192 - 1199. [Abstract] [Full Text] [PDF]

				T. N Hilliard, N. Regamey, J. K Shute, A. G Nicholson, E. W F W Alton, A. Bush, and J. C Davies Airway remodelling in children with cystic fibrosis Thorax, December 1, 2007; 62(12): 1074 - 1080. [Abstract] [Full Text] [PDF]

				R. Vepachedu, M. M. Gorska, N. Singhania, G. P. Cosgrove, K. K. Brown, and R. Alam Unc119 Regulates Myofibroblast Differentiation through the Activation of Fyn and the p38 MAPK Pathway J. Immunol., July 1, 2007; 179(1): 682 - 690. [Abstract] [Full Text] [PDF]

				S. Xie, M. B. Sukkar, R. Issa, N. M. Khorasani, and K. F. Chung Mechanisms of induction of airway smooth muscle hyperplasia by transforming growth factor-beta Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L245 - L253. [Abstract] [Full Text] [PDF]

				I. H. Heijink, P. M. Kies, H. F. Kauffman, D. S. Postma, A. J. M. van Oosterhout, and E. Vellenga Down-Regulation of E-Cadherin in Human Bronchial Epithelial Cells Leads to Epidermal Growth Factor Receptor-Dependent Th2 Cell-Promoting Activity J. Immunol., June 15, 2007; 178(12): 7678 - 7685. [Abstract] [Full Text] [PDF]

				A. V. Le, J. Y. Cho, M. Miller, S. McElwain, K. Golgotiu, and D. H. Broide Inhibition of Allergen-Induced Airway Remodeling in Smad 3-Deficient Mice J. Immunol., June 1, 2007; 178(11): 7310 - 7316. [Abstract] [Full Text] [PDF]

				A. Sturrock, T. P. Huecksteadt, K. Norman, K. Sanders, T. M. Murphy, P. Chitano, K. Wilson, J. R. Hoidal, and T. P. Kennedy Nox4 mediates TGF-beta1-induced retinoblastoma protein phosphorylation, proliferation, and hypertrophy in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1543 - L1555. [Abstract] [Full Text] [PDF]

				K. L. McCann and F. Imani Transforming Growth Factor {beta} Enhances Respiratory Syncytial Virus Replication and Tumor Necrosis Factor Alpha Induction in Human Epithelial Cells J. Virol., March 15, 2007; 81(6): 2880 - 2886. [Abstract] [Full Text] [PDF]

				K.-Y. Lee, S.-C. Ho, H.-C. Lin, S.-M. Lin, C.-Y. Liu, C.-D. Huang, C.-H. Wang, K. F. Chung, and H.-P. Kuo Neutrophil-Derived Elastase Induces TGF-beta1 Secretion in Human Airway Smooth Muscle via NF-{kappa}B Pathway Am. J. Respir. Cell Mol. Biol., October 1, 2006; 35(4): 407 - 414. [Abstract] [Full Text] [PDF]

				Y. Bosse, C. Thompson, J. Stankova, and M. Rola-Pleszczynski Fibroblast Growth Factor 2 and Transforming Growth Factor beta1 Synergism in Human Bronchial Smooth Muscle Cell Proliferation Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 746 - 753. [Abstract] [Full Text] [PDF]

				C. Boxall, S. T. Holgate, and D. E. Davies The contribution of transforming growth factor-{beta} and epidermal growth factor signalling to airway remodelling in chronic asthma Eur. Respir. J., January 1, 2006; 27(1): 208 - 229. [Abstract] [Full Text] [PDF]

				M. Miller, J. Y. Cho, K. McElwain, S. McElwain, J. Y. Shim, M. Manni, J. S. Baek, and D. H. Broide Corticosteroids prevent myofibroblast accumulation and airway remodeling in mice Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L162 - L169. [Abstract] [Full Text] [PDF]

				D.-W. Perng, Y.-C. Wu, K.-T. Chang, M.-T. Wu, Y.-C. Chiou, K.-C. Su, R.-P. Perng, and Y.-C. Lee Leukotriene C4 Induces TGF-{beta}1 Production in Airway Epithelium via p38 Kinase Pathway Am. J. Respir. Cell Mol. Biol., January 1, 2006; 34(1): 101 - 107. [Abstract] [Full Text] [PDF]

				P. R. A. Johnson, J. K. Burgess, Q. Ge, M. Poniris, S. Boustany, S. M. Twigg, and J. L. Black Connective Tissue Growth Factor Induces Extracellular Matrix in Asthmatic Airway Smooth Muscle Am. J. Respir. Crit. Care Med., January 1, 2006; 173(1): 32 - 41. [Abstract] [Full Text] [PDF]

				J. K. Burgess, Q. Ge, M. H. Poniris, S. Boustany, S. M. Twigg, J. L. Black, and P. R. A. Johnson Connective tissue growth factor and vascular endothelial growth factor from airway smooth muscle interact with the extracellular matrix Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L153 - L161. [Abstract] [Full Text] [PDF]

				C. Bronner Is the upregulation of bradykinin B2 receptors by TGF-{beta}1 one of the missing pieces in the "airway hyperresponsiveness" puzzle? Am J Physiol Lung Cell Mol Physiol, October 1, 2005; 289(4): L509 - L510. [Full Text] [PDF]

				J. H. Kim, D. Jain, O. Tliba, B. Yang, W. F. Jester Jr., R. A. Panettieri Jr., Y. Amrani, and E. Pure TGF-{beta} potentiates airway smooth muscle responsiveness to bradykinin Am J Physiol Lung Cell Mol Physiol, October 1, 2005; 289(4): L511 - L520. [Abstract] [Full Text] [PDF]

				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]

				S. J. McMillan, G. Xanthou, and C. M. Lloyd Manipulation of Allergen-Induced Airway Remodeling by Treatment with Anti-TGF-{beta} Antibody: Effect on the Smad Signaling Pathway J. Immunol., May 1, 2005; 174(9): 5774 - 5780. [Abstract] [Full Text] [PDF]

				M. M. Kelly, R. Leigh, P. Bonniaud, R. Ellis, J. Wattie, M. J. Smith, G. Martin, M. Panju, M. D. Inman, and J. Gauldie Epithelial Expression of Profibrotic Mediators in a Model of Allergen-Induced Airway Remodeling Am. J. Respir. Cell Mol. Biol., February 1, 2005; 32(2): 99 - 107. [Abstract] [Full Text] [PDF]

				S. Xie, M. B. Sukkar, R. Issa, U. Oltmanns, A. G. Nicholson, and K. F. Chung Regulation of TGF-{beta}1-induced connective tissue growth factor expression in airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L68 - L76. [Abstract] [Full Text] [PDF]

				R. Aghanouri, M. Ghanei, J. Aslani, H. Keivani-Amine, F. Rastegar, and A. Karkhane Fibrogenic cytokine levels in bronchoalveolar lavage aspirates 15 years after exposure to sulfur mustard Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1160 - L1164. [Abstract] [Full Text] [PDF]

				N. S. Undevia, D. R. Dorscheid, B. A. Marroquin, W. L. Gugliotta, R. Tse, and S. R. White Smad and p38-MAPK signaling mediates apoptotic effects of transforming growth factor-{beta}1 in human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, September 1, 2004; 287(3): L515 - L524. [Abstract] [Full Text] [PDF]

				T. Kikuchi, J. D. Shively, J. S. Foley, J. M. Drazen, and D. J. Tschumperlin Differentiation-dependent responsiveness of bronchial epithelial cells to IL-4/13 stimulation Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L119 - L126. [Abstract] [Full Text] [PDF]

				J. Y. Cho, M. Miller, K. J. Baek, J. W. Han, J. Nayar, M. Rodriguez, S. Y. Lee, K. McElwain, S. McElwain, E. Raz, et al. Immunostimulatory DNA Inhibits Transforming Growth Factor-{beta} Expression and Airway Remodeling Am. J. Respir. Cell Mol. Biol., May 1, 2004; 30(5): 651 - 661. [Abstract] [Full Text] [PDF]

				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]

				M. Terada, E. A. B. Kelly, and N. N. Jarjour Increased Thrombin Activity after Allergen Challenge: A Potential Link to Airway Remodeling? Am. J. Respir. Crit. Care Med., February 1, 2004; 169(3): 373 - 377. [Abstract] [Full Text] [PDF]

				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. Transforming Growth Factor-{beta}1 Promoter Polymorphism C-509T Is Associated with Asthma Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 214 - 219. [Abstract] [Full Text] [PDF]

				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]

				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]

				N J Kenyon, R W Ward, G McGrew, and J A Last TGF-{beta}1 causes airway fibrosis and increased collagen I and III mRNA in mice Thorax, September 1, 2003; 58(9): 772 - 777. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				S. M. Puddicombe, C. Torres-Lozano, A. Richter, F. Bucchieri, J. L. Lordan, P. H. Howarth, B. Vrugt, R. Albers, R. Djukanovic, S. T. Holgate, et al. Increased Expression of p21waf Cyclin-Dependent Kinase Inhibitor in Asthmatic Bronchial Epithelium Am. J. Respir. Cell Mol. Biol., January 1, 2003; 28(1): 61 - 68. [Abstract] [Full Text] [PDF]

				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]

				D. A. Bradbury, R. Newton, Y.-M. Zhu, J. Stocks, L. Corbett, E. D. Holland, L. H. Pang, and A. J. Knox Effect of bradykinin, TGF-beta 1, IL-1beta , and hypoxia on COX-2 expression in pulmonary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L717 - L725. [Abstract] [Full Text] [PDF]

				A. Rosendahl, E. Pardali, M. Speletas, P. ten Dijke, C.-H. Heldin, and P. Sideras Activation of Bone Morphogenetic Protein/Smad Signaling in Bronchial Epithelial Cells during Airway Inflammation Am. J. Respir. Cell Mol. Biol., August 1, 2002; 27(2): 160 - 169. [Abstract] [Full Text] [PDF]

				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]

				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]

				A. T. HASTIE, W. K. KRAFT, K. B. NYCE, J. G. ZANGRILLI, A. I. MUSANI, J. E. FISH, and S. P. PETERS Asthmatic Epithelial Cell Proliferation and Stimulation of Collagen Production . Human Asthmatic Epithelial Cells Stimulate Collagen Type III Production by Human Lung Myofibroblasts after Segmental Allergen Challenge Am. J. Respir. Crit. Care Med., January 15, 2002; 165(2): 266 - 272. [Abstract] [Full Text] [PDF]

				W. J. Howat, S. T. Holgate, and P. M. Lackie TGF-beta isoform release and activation during in vitro bronchial epithelial wound repair Am J Physiol Lung Cell Mol Physiol, January 1, 2002; 282(1): L115 - L123. [Abstract] [Full Text] [PDF]

				T. J. Kelley, H. L. Elmer, and D. A. Corey Reduced Smad3 Protein Expression and Altered Transforming Growth Factor-beta 1-Mediated Signaling in Cystic Fibrosis Epithelial Cells Am. J. Respir. Cell Mol. Biol., December 1, 2001; 25(6): 732 - 738. [Abstract] [Full Text] [PDF]

				A. Richter, S. M. Puddicombe, J. L. Lordan, F. Bucchieri, S. J. Wilson, R. Djukanovic', G. Dent, S. T. Holgate, and D. E. Davies The Contribution of Interleukin (IL)-4 and IL-13 to the Epithelial-Mesenchymal Trophic Unit in Asthma Am. J. Respir. Cell Mol. Biol., September 1, 2001; 25(3): 385 - 391. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				C. Y. Fong, L. Pang, E. Holland, and A. J. Knox TGF-beta 1 stimulates IL-8 release, COX-2 expression, and PGE2 release in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, July 1, 2000; 279(1): L201 - L207. [Abstract] [Full Text] [PDF]

				J. BOUSQUET, P. K. JEFFERY, W. W. BUSSE, M. JOHNSON, and A. M. VIGNOLA Asthma . From Bronchoconstriction to Airways Inflammation and Remodeling Am. J. Respir. Crit. Care Med., May 1, 2000; 161(5): 1720 - 1745. [Full Text]

				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 Am J Physiol Lung Cell Mol Physiol, March 1, 2000; 278(3): L545 - L551. [Abstract] [Full Text] [PDF]

				E. T. NAURECKAS, I. MAURICE NDUKWU, A. J. HALAYKO, C. MAXWELL, M. B. HERSHENSON, and J. SOLWAY Bronchoalveolar Lavage Fluid from Asthmatic Subjects Is Mitogenic for Human Airway Smooth Muscle Am. J. Respir. Crit. Care Med., December 1, 1999; 160(6): 2062 - 2066. [Abstract] [Full Text]

				K F Chung and P J Barnes Cytokines in asthma Thorax, September 1, 1999; 54(9): 825 - 857. [Full Text]

<