Abstract/Details

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


2004 2004

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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)


Subject
Biology;
Molecular biology
Classification
0306: Biology
0307: Molecular biology
Identifier / keyword
Biological sciences; BAEC; Bronchial airway epithelial cell; Denudation; Asthma; IL-4; IL-13
Title
Bronchial airway epithelial cell denudation in the pathogenesis of asthma: The role of IL-4 and IL-13
Author
Ramirez-Icaza, Gail
Number of pages
118
Publication year
2004
Degree date
2004
School code
0094
Source
DAI-B 68/10, Apr 2008
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780549286028
Advisor
Johnson, Mary T.
University/institution
Indiana State University
University location
United States -- Indiana
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3286439
ProQuest document ID
305196858
Copyright
Copyright ProQuest, UMI Dissertations Publishing 2004
Document URL
http://search.proquest.com/docview/305196858
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