Wound Healing in Sinonasal Mucosa: Influence of Th2 Inflammatory Mediators Pubblico
Wise, Sarah K (2012)
Abstract
ABSTRACT
Wound Healing in Sinonasal Mucosa: Influence of Th2 Inflammatory
Mediators
Background: Inflammatory rhinosinusitis affects over 29
million U.S. adults. Prolonged healing
and persistent inflammation following surgery for rhinosinusitis
impact quality of life and
healthcare resources. Chronic rhinosinusitis (CRS) is categorized
as Th1, classically infectious, or
Th2, classically allergic with elevated interleukins (IL)-4, 5, and
13. Prior studies demonstrate
decreased wound healing with Th2 inflammatory mediator exposure,
but this is not extensively
studied in sinonasal epithelium.
Hypothesis: Exposure of sinonasal epithelial cell layers
in vitro to characteristic Th2
inflammatory cytokines IL-4, IL-5, and IL-13 (separately) will
impair wound healing rates and
decrease expression of specifically-chosen epithelial migratory and
intercellular adherens
junction proteins compared to control sinonasal epithelial wounds
not exposed to cytokines.
Methods: Following 24-hour exposure to IL-4, 5, or 13 versus
controls, sterile linear mechanical
wounds were created in primary sinonasal epithelial cultures (n =
12 wounds per condition).
Wounds were followed for 36 hours or until complete closure and
wound areas calculated by
image analysis. Group differences in epithelial migratory proteins
annexin 2, vinculin, and β1-
inegrin and adherens junction proteins E-cadherin and
β-catenin were assessed by
immunofluorescence labeling, confocal microscopy, and Western
immunoblots. Baseline
epithelial protein differences ruled out by immunofluorescence and
Western immunoblots.
Results: Significant wound closure differences were
identified across cytokine exposure groups
(p<0.001). A significant time-group interaction in wound closure
was demonstrated by repeated
measures ANOVA (p<0.001). At 36-hours, 75% of wounds exposed to
IL-4 were incompletely
closed, whereas 25% of control wounds remained open. With IL-4
exposure, annexin 2 and
vinculin at wound edges were decreased versus no-cytokine exposure
control (p<0.01).
Conclusions: Th2 cytokine IL-4 decreases sinonasal
epithelial wound closure in vitro. Wound
edge migratory proteins are diminished with IL-4 exposure. This
supports the hypothesis that Th2
exposure impairs sinonasal epithelial wound healing.
Table of Contents
TABLE OF CONTENTS
Introduction
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1
Background
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3
Methods
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7
Results
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19
Discussion
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26
Conclusions
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32
Future Directions
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33
References
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34
Figures and Tables
Figure 1
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40
Figure 2
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41
Figure 3
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42
Figure 4
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44
Figure 5
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Table 1
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48
Figure 6
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50
Table 2
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52
Figure 7
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54
Table 3
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56
Figure 8
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Figure 9
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Table 4
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65
Figure 10
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66
Figure 11
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69
Figure 12
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73
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