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THE ROLE OF TREFOIL FACTOR (TFF)-2 ALLERGEN-INDUCED MUCOSAL INFLAMMATION

NIKOLAIDIS, NIKOLAOS
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1172858094

Abstract Details

2007, PhD, University of Cincinnati, Medicine : Cell and Molecular Biology.
Allergen-induced mucosal inflammation is a complex process involving a localized pathologic Th2 response. In this thesis, we examine the role of trefoil factor (TFF)2, a gene upregulated in response to allergen challenge in the lung and a major component of the mucosal layer in the gastrointestinal tract, in allergen-induced mucosal inflammation. Employing animal models of allergen-induced pulmonary inflammation we identify TFF2 as an allergen-induced gene product differentially regulated by Th2 cytokines and STAT6. Our findings also demonstrate that TFF2 expression is induced early following allergen challenge and that this induction is maintained for two weeks following allergen challenge in the lung. We also identify that TFF2 expression in the allergen challenged lung is localized to airway epithelial cells which have differentiated into the mucus producing goblet cell phenotype. Through the use of TFF2 gene deleted mice, we were able to establish that the loss of TFF2 does not alter the induction or resolution of mucus cell metaplasia following allergen challenge. Thus, TFF2 is an allergen-induced gene, which is expressed in mucus positive airways, but is not a major contributor to allergen-induced goblet cell metaplasia, mucus production, or inflammatory responses in the lung. Importantly, the loss of TFF2 does result in a modest yet significant decrease in total BALF cellularity following allergen challenge. To further examine the role of TFF2 in mucosal inflammation, an animal model of intestinal anaphylaxis was characterized. Gastrointestinal allergy resulting in intestinal anaphylaxis is a complex intestinal disorder characterized by a localized Th2 response, and is dependent on IgE-mediated mast cell degranulation, although early events following allergen ingestion and processing remain poorly understood. Here we show for the first time that TFF2 deficiency results in a delay of intestinal anaphylaxis as measured by diarrhea. Notably, intestinal mast cell levels and serum levels of mMCP-1 show delayed increases to allergen challenge in TFF2 gene deleted mice. Thus, TFF2 gene deleted mice have increased resistance to allergen induced intestinal anaphylaxis possibly due to alterations in the immune response. Collectively, we provide evidence that TFF2 may act to modulate the immune response to allergen challenge, but is not a major regulator of mucosal inflammation.
Dr. Marc Rothenberg (Advisor)
137 p.

Recommended Citations

Citations

  • NIKOLAIDIS, N. (2007). THE ROLE OF TREFOIL FACTOR (TFF)-2 ALLERGEN-INDUCED MUCOSAL INFLAMMATION [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1172858094

    APA Style (7th edition)

  • NIKOLAIDIS, NIKOLAOS. THE ROLE OF TREFOIL FACTOR (TFF)-2 ALLERGEN-INDUCED MUCOSAL INFLAMMATION. 2007. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1172858094.

    MLA Style (8th edition)

  • NIKOLAIDIS, NIKOLAOS. "THE ROLE OF TREFOIL FACTOR (TFF)-2 ALLERGEN-INDUCED MUCOSAL INFLAMMATION." Doctoral dissertation, University of Cincinnati, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1172858094

    Chicago Manual of Style (17th edition)

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© 2007, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.