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Published ahead of print on April 17, 2003, doi:10.1165/rcmb.2002-0309OC

Am. J. Respir. Cell Mol. Biol., Volume 29, Number 4, October 2003, 458-464

A more recent version of this article appeared on October 1, 2003
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Submitted on December 20, 2002
Revised on April 16, 2003

Trefoil factor-2 is an allergen-induced gene regulated by TH2 cytokines and STAT6 in the lung

Nikolaos M Nikolaidis1, Nives Zimmermann2, Nina E King2, Anil Mishra2, Samuel M Pope3, Fred D Finkelman4, and Marc E Rothenberg2*

1 Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA, 2 Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA, 3 Molecular Genetics, University of Cincinnati, Cincinnati, OH, USA, 4 Internal Medicine, University of Cincinnati, Cincinnati, OH, USA; Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

* To whom correspondence should be addressed. 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 pharmacological delivery and transgenic overexpression, TFF2 was demonstrated to be strongly induced in the lung by IL-4 and IL-13. Notably, TFF2 induction by both OVA and pharmacological delivery of IL-4 and IL-13 was dependent upon signal-transducer-and-activator-of-transcription (STAT6). 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.




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Copyright © 2003 American Thoracic Society. 		  2009 ATS Conference