| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
School of Medicine, Respiratory Cell and Molecular Biology Division, Southampton General Hospital, Southampton, United Kingdom
In sensitized individuals, exposure to allergens such as
Dermatophagoides pteronyssinus (Der p)
causes Th2 polarization and release of cytokines, including IL-4 and
IL-13. Because Der p extracts also have direct effects
on epithelial cells, we hypothesized that allergen augments the effects
of Th2 cytokines by promoting mediator release from the bronchial
epithelium in allergic asthma. To test our hypothesis, primary
bronchial epithelial cultures were grown from bronchial brushings of
normal and atopic asthmatic subjects. RT-PCR showed that each culture
expressed IL-4R
, common 
-chain, and
IL-13R1, as well as IL-13R2, which
negatively regulates IL-13 signaling; FACS analysis confirmed
IL-13R2 protein expression. Exposure of epithelial
cultures to either Der p extracts, TNF-, IL-4, or
IL-13 enhanced GM-CSF and IL-8 release, and this was partially
suppressible by corticosteroids. Simultaneous exposure of the
epithelial cultures to IL-4 or IL-13 together with Der p
resulted in a further increase in cytokine release, which was at least
additive. Release of TGF- was also increased by TNF- and
combinations of IL-4, IL-13, and Der p; however, this
stimulation was only significant in the asthma-derived cultures. These
data suggest that, in an allergic environment, Th2 cytokines and
allergen have the potential to sustain airway inflammation through a
cooperative effect on cytokine release by the bronchial epithelium. Our
novel finding that IL-4, IL-13, and allergen enhance release of
TGF-, a ligand for the epidermal growth factor receptor that
stimulates fibroblast proliferation and goblet cell differentiation,
provides a potential link between allergen exposure, Th2 cytokines, and
airway remodelling in asthma.
This article has been cited by other articles:
|
|
 |
|
  S. R. White, L. D. Martin, M. K. Abe, B. A. Marroquin, R. Stern, and X. Fu Insulin receptor substrate-1/2 mediates IL-4-induced migration of human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, July 1, 2009; 297(1): L164 - L173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. McDougall, M. G. Blaylock, J. G. Douglas, R. J. Brooker, P. J. Helms, and G. M. Walsh Nasal Epithelial Cells as Surrogates for Bronchial Epithelial Cells in Airway Inflammation Studies Am. J. Respir. Cell Mol. Biol., November 1, 2008; 39(5): 560 - 568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. M. Farghaly, I. S. Blagbrough, D. A. Medina-Tato, and M. L. Watson Interleukin 13 Increases Contractility of Murine Tracheal Smooth Muscle by a Phosphoinositide 3-kinase p110{delta}-Dependent Mechanism Mol. Pharmacol., May 1, 2008; 73(5): 1530 - 1537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Uddin, G. Seumois, L. C. Lau, P. Rytila, D. E. Davies, and R. Djukanovic Enhancement of neutrophil function by the bronchial epithelium stimulated by epidermal growth factor Eur. Respir. J., April 1, 2008; 31(4): 714 - 724. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
I. H. Heijink, P. Marcel Kies, A. J. M. van Oosterhout, D. S. Postma, H. F. Kauffman, and E. Vellenga Der p, IL-4, and TGF-beta Cooperatively Induce EGFR-Dependent TARC Expression in Airway Epithelium Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 351 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Cameron, R. B. Webster, J. M. Strempel, P. Kiesler, M. Kabesch, H. Ramachandran, L. Yu, D. A. Stern, P. E. Graves, I. C. Lohman, et al. Th2 Cell-Selective Enhancement of Human IL13 Transcription by IL13-1112C>T, a Polymorphism Associated with Allergic Inflammation J. Immunol., December 15, 2006; 177(12): 8633 - 8642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. F. Chung Intrinsic differences of the airway epithelium in childhood allergic asthma. Am. J. Respir. Crit. Care Med., November 15, 2006; 174(10): 1066 - 1067. [Full Text] [PDF]
|
|
|
|
|
|
A.-L. Andrews, J. W. Holloway, S. T. Holgate, and D. E. Davies IL-4 Receptor {alpha} Is an Important Modulator of IL-4 and IL-13 Receptor Binding: Implications for the Development of Therapeutic Targets. J. Immunol., June 15, 2006; 176(12): 7456 - 7461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
I. A. Forrest, D. M. Murphy, C. Ward, D. Jones, G. E. Johnson, L. Archer, F. K. Gould, T. E. Cawston, J. L. Lordan, and P. A. Corris Primary airway epithelial cell culture from lung transplant recipients Eur. Respir. J., December 1, 2005; 26(6): 1080 - 1085. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Ward, I A Forrest, D M Murphy, G E Johnson, H Robertson, T E Cawston, A J Fisher, J H Dark, J L Lordan, J A Kirby, et al. Phenotype of airway epithelial cells suggests epithelial to mesenchymal cell transition in clinically stable lung transplant recipients Thorax, October 1, 2005; 60(10): 865 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lindstedt, A. Schiott, A. Bengtsson, K. Larsson, M. Korsgren, L. Greiff, and C. A. K. Borrebaeck Genomic and functional delineation of dendritic cells and memory T cells derived from grass pollen-allergic patients and healthy individuals Int. Immunol., April 1, 2005; 17(4): 401 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A.B. Wark, S. L. Johnston, F. Bucchieri, R. Powell, S. Puddicombe, V. Laza-Stanca, S. T. Holgate, and D. E. Davies Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus J. Exp. Med., March 21, 2005; 201(6): 937 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Bouzigon, M.-H. Dizier, C. Krahenbuhl, A. Lemainque, I. Annesi-Maesano, C. Betard, J. Bousquet, D. Charpin, F. Gormand, M. Guilloud-Bataille, et al. Clustering patterns of LOD scores for asthma-related phenotypes revealed by a genome-wide screen in 295 French EGEA families Hum. Mol. Genet., December 15, 2004; 13(24): 3103 - 3113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yamamoto, I. Kobayashi, K. Tsuji, N. Nishi, E. Muro, M. Miyazaki, M. Zaitsu, S. Inada, T. Ichimaru, and Y. Hamasaki Upregulation of Interleukin-4 Receptor by Interferon-{gamma}: Enhanced Interleukin-4-Induced Eotaxin-3 Production in Airway Epithelium Am. J. Respir. Cell Mol. Biol., October 1, 2004; 31(4): 456 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hoshino, T. Tsuji, J. Matsuzaki, T. Jinushi, S. Ashino, T. Teramura, K. Chamoto, Y. Tanaka, Y. Asakura, T. Sakurai, et al. STAT6-mediated signaling in Th2-dependent allergic asthma: critical role for the development of eosinophilia, airway hyper-responsiveness and mucus hypersecretion, distinct from its role in Th2 differentiation Int. Immunol., October 1, 2004; 16(10): 1497 - 1505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. D. Le Cras, W. D. Hardie, G. H. Deutsch, K. H. Albertine, M. Ikegami, J. A. Whitsett, and T. R. Korfhagen Transient induction of TGF-{alpha} disrupts lung morphogenesis, causing pulmonary disease in adulthood Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L718 - L729. [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]
|
|
|
|
 |
|
 S.T. Holgate Lessons learnt from the epidemic of asthma QJM, May 1, 2004; 97(5): 247 - 257. [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]
|
|
|
|
|
|
W. D. Hardie, T. D. Le Cras, K. Jiang, J. W. Tichelaar, M. Azhar, and T. R. Korfhagen Conditional expression of transforming growth factor-{alpha} in adult mouse lung causes pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L741 - L749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. D. Le Cras, W. D. Hardie, K. Fagan, J. A. Whitsett, and T. R. Korfhagen Disrupted pulmonary vascular development and pulmonary hypertension in transgenic mice overexpressing transforming growth factor-{alpha} Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L1046 - L1054. [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]
|
|
|
|
|
|
I.S. Patel, N.J. Roberts, S.J. Lloyd-Owen, R.J. Sapsford, and J.A. Wedzicha Airway epithelial inflammatory responses and clinical parameters in COPD Eur. Respir. J., July 1, 2003; 22(1): 94 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Stick and P. G. Holt The Airway Epithelium as Immune Modulator: The LARC Ascending Am. J. Respir. Cell Mol. Biol., June 1, 2003; 28(6): 641 - 644. [Full Text] [PDF]
|
|
|
|
|
|
N. Asokananthan, P. T. Graham, D. J. Stewart, A. J. Bakker, K. A. Eidne, P. J. Thompson, and G. A. Stewart House Dust Mite Allergens Induce Proinflammatory Cytokines from Respiratory Epithelial Cells: The Cysteine Protease Allergen, Der p 1, Activates Protease-Activated Receptor (PAR)-2 and Inactivates PAR-1 J. Immunol., October 15, 2002; 169(8): 4572 - 4578. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
