help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on April 17, 2003, doi:10.1165/rcmb.2002-0309OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2002-0309OCv1
29/4/458    most recent
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 Nikolaidis, N. M.
Right arrow Articles by Rothenberg, M. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nikolaidis, N. M.
Right arrow Articles by Rothenberg, M. E.
American Journal of Respiratory Cell and Molecular Biology. Vol. 29, pp. 458-464, 2003
© 2003 American Thoracic Society
DOI: 10.1165/rcmb.2002-0309OC

Trefoil Factor-2 Is an Allergen-Induced Gene Regulated by Th2 Cytokines and STAT6 in the Lung

Nikolaos M. Nikolaidis, Nives Zimmermann, Nina E. King, Anil Mishra, Samuel M. Pope, Fred D. Finkelman and Marc E. Rothenberg

Departments of Cell Biology, Molecular Genetics, and Internal Medicine, Division of Immunology, University of Cincinnati College of Medicine; and Divisions of Allergy and Immunology, and Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

Address correspondence to: Marc Rothenberg, M.D., Ph.D., Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7028 Cincinnati, OH 45229. E-mail: Rothenberg{at}cchmc.org

Asthma, a complex chronic inflammatory pulmonary disorder, is on the rise despite intense ongoing research, underscoring the need for new scientific inquiry. In an effort to provide unbiased insight into the pathogenesis of this disease, we took an empirical approach involving transcript expression profiling of lung tissue from mice with experimental asthma. Employing asthma models induced by different allergens (ovalbumin [OVA] and Aspergillus fumigatus), we found strong induction of trefoil factor-2 (TFF2), a gene involved in epithelial restitution and mucosal secretion in the gastrointestinal tract. Using a combination of pharmacologic delivery and transgenic overexpression, TFF2 was demonstrated to be strongly induced in the lung by interleukin (IL)-4 and IL-13. Notably, TFF2 induction by both OVA and pharmacologic delivery of IL-4 and IL-13 was dependent upon signal transducer and activator of transcription (STAT)6. However, the upregulation of TFF2 by both chronic expression of IL-4 and Aspergillus fumigatus antigen was independent of STAT6. These results establish that TFF2 is an allergen-induced lung gene product differentially regulated by Th2 cytokines and STAT6. Given the important role of trefoil factors in wound healing, epithelial restitution, and maintenance of mucosal integrity in the gastrointestinal tract, these results support a potential role for TFF2, in both the acute and chronic phase of experimental asthma, via separate induction pathways.

Abbreviations: Airway hyperreactivity, AHR • interleukin, IL • ovalbumin, OVA • signal transducer and activator of transcription, STAT • T helper 2 lymphocytes, Th2 cells • trefoil factor, TFF




This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
C. C. Lewis, J. Y. H. Yang, X. Huang, S. K. Banerjee, M. R. Blackburn, P. Baluk, D. M. McDonald, T. S. Blackwell, V. Nagabhushanam, W. Peters, et al.
Disease-Specific Gene Expression Profiling in Multiple Models of Lung Disease
Am. J. Respir. Crit. Care Med., February 15, 2008; 177(4): 376 - 387.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
K. Ganguly, T. Stoeger, S. C. Wesselkamper, C. Reinhard, M. A. Sartor, M. Medvedovic, C. R. Tomlinson, I. Bolle, J. M. Mason, G. D. Leikauf, et al.
Candidate genes controlling pulmonary function in mice: transcript profiling and predicted protein structure
Physiol Genomics, November 14, 2007; 31(3): 410 - 421.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. Munitz, I. Bachelet, F. D. Finkelman, M. E. Rothenberg, and F. Levi-Schaffer
CD48 Is Critically Involved in Allergic Eosinophilic Airway Inflammation
Am. J. Respir. Crit. Care Med., May 1, 2007; 175(9): 911 - 918.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
I. Kouznetsova, C. E. Chwieralski, R. Balder, M. Hinz, A. Braun, N. Krug, and W. Hoffmann
Induced Trefoil Factor Family 1 Expression by Trans-Differentiating Clara Cells in a Murine Asthma Model
Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 286 - 295.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
E. A. Kurt-Jones, L. Cao, F. Sandor, A. B. Rogers, M. T. Whary, P. R. Nambiar, A. Cerny, G. Bowen, J. Yan, S. Takaishi, et al.
Trefoil Family Factor 2 Is Expressed in Murine Gastric and Immune Cells and Controls both Gastrointestinal Inflammation and Systemic Immune Responses
Infect. Immun., January 1, 2007; 75(1): 471 - 480.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
J. J. Reece, M. C. Siracusa, and A. L. Scott
Innate Immune Responses to Lung-Stage Helminth Infection Induce Alternatively Activated Alveolar Macrophages
Infect. Immun., September 1, 2006; 74(9): 4970 - 4981.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
A. L. Greene, M. S. Rutherford, R. R. Regal, G. H. Flickinger, J. A. Hendrickson, C. Giulivi, M. E. Mohrman, D. G. Fraser, and J. F. Regal
Arginase Activity Differs with Allergen in the Effector Phase of Ovalbumin- versus Trimellitic Anhydride-Induced Asthma
Toxicol. Sci., December 1, 2005; 88(2): 420 - 433.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
C K Haston, T G Tomko, N Godin, L Kerckhoff, and M T Hallett
Murine candidate bleomycin induced pulmonary fibrosis susceptibility genes identified by gene expression and sequence analysis of linkage regions
J. Med. Genet., June 1, 2005; 42(6): 464 - 473.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
N. Zimmermann, M. P. Doepker, D. P. Witte, K. F. Stringer, P. C. Fulkerson, S. M. Pope, E. B. Brandt, A. Mishra, N. E. King, N. M. Nikolaidis, et al.
Expression and Regulation of Small Proline-Rich Protein 2 in Allergic Inflammation
Am. J. Respir. Cell Mol. Biol., May 1, 2005; 32(5): 428 - 435.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
C. E. Chwieralski, I. Schnurra, L. Thim, and W. Hoffmann
Epidermal Growth Factor and Trefoil Factor Family 2 Synergistically Trigger Chemotaxis on BEAS-2B Cells via Different Signaling Cascades
Am. J. Respir. Cell Mol. Biol., November 1, 2004; 31(5): 528 - 537.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
U. Forssmann, I. Hartung, R. Balder, B. Fuchs, S. E. Escher, N. Spodsberg, Y. Dulkys, M. Walden, A. Heitland, A. Braun, et al.
n-Nonanoyl-CC Chemokine Ligand 14, a Potent CC Chemokine Ligand 14 Analogue That Prevents the Recruitment of Eosinophils in Allergic Airway Inflammation
J. Immunol., September 1, 2004; 173(5): 3456 - 3466.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Zimmermann, A. Mishra, N. E. King, P. C. Fulkerson, M. P. Doepker, N. M. Nikolaidis, L. E. Kindinger, E. A. Moulton, B. J. Aronow, and M. E. Rothenberg
Transcript Signatures in Experimental Asthma: Identification of STAT6-Dependent and -Independent Pathways
J. Immunol., February 1, 2004; 172(3): 1815 - 1824.
[Abstract] [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.