Bronchial airway epithelial cell denudation in the pathogenesis of asthma: The role of IL-4 and IL-13

2004 2004

Other formats:

At the request of the author, this graduate work is not available to view or purchase.

Abstract (summary)

Asthma is characterized by infiltration and shedding of the bronchial epithelium. The Th2 cytokines IL-4 and IL-13 are involved in the cellular recruitment and infiltration seen in asthma. The effects of IL-4 and IL-13 on cell-matrix interactions, gap formation, increased monolayer permeability and epithelial shedding are unknown. Experiments described in this report test the hypothesis that bronchial airway epithelial cells (BAEC) express paxillin, a structural focal adhesion protein, and down-regulation of paxillin by Th2 cytokines lead to BAEC hyperpermeability. Furthermore, the hypothesis that the Th2 cytokines IL-4 and IL-13 could down-regulate the adherens junction proteins β-catenin and E-cadherin in BAEC, and that this decrease in β-catenin and E-cadherin also may play a role in BAEC hyperpermeability was tested. The presence of paxillin in BAEC was shown by confocal microscopy which also demonstrated gap formation in IL4 and IL-13-stimulated BAEC confluent monolayers that stained positive for β-catenin and E-cadherin. Western blot analysis demonstrated that IL-4 and IL-13 stimulation results in down-regulation of paxillin, β-catenin and E-cadherin production. IL-4 and IL-13 stimulation decreased epithelial cell-matrix attachment as measured by electrical cell-substrate impedance sensing system. IL-4 and IL-13 stimulation increased BAEC monolayer permeability as measured by Evans blue dye/BSA protein leak assay. These results suggest that Th2 cytokines IL-4 and IL-13 down-regulate paxillin production by BAEC, thereby disrupting the cell-matrix interactions. These results also suggest that IL-4 and IL-13 down-regulate β-catenin and E-cadherin production by BAEC, induce gap formation and promote monolayer hyperpermeability. In conclusion, the Th2 cytokines IL-4 and IL-13 appear to disrupt cell-cell and cell-matrix interactions within the bronchial epithelium. This may help explain the epithelial shedding and epithelial membrane hyperpermeability that occurs in asthma.

Indexing (details)

Molecular biology
0306: Biology
0307: Molecular biology
Identifier / keyword
Biological sciences; BAEC; Bronchial airway epithelial cell; Denudation; Asthma; IL-4; IL-13
Bronchial airway epithelial cell denudation in the pathogenesis of asthma: The role of IL-4 and IL-13
Ramirez-Icaza, Gail
Number of pages
Publication year
Degree date
School code
DAI-B 68/10, Apr 2008
Place of publication
Ann Arbor
Country of publication
United States
Johnson, Mary T.
Indiana State University
University location
United States -- Indiana
Source type
Dissertations & Theses
Document type
Dissertation/thesis number
ProQuest document ID
Copyright ProQuest, UMI Dissertations Publishing 2004
Document URL
Access the complete full text

You can get the full text of this document if it is part of your institution's ProQuest subscription.

Try one of the following:

  • Connect to ProQuest through your library network and search for the document from there.
  • Request the document from your library.
  • Go to the ProQuest login page and enter a ProQuest or My Research username / password.