Wound Healing in Sinonasal Mucosa: Influence of Th2 Inflammatory Mediators 公开

Wise, Sarah K (2012)

Permanent URL: https://etd.library.emory.edu/concern/etds/2514nm291?locale=zh
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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 ........................................................................................................................ 1
Background ........................................................................................................................ 3
Methods .............................................................................................................................. 7
Results ................................................................................................................................ 19
Discussion .......................................................................................................................... 26
Conclusions ........................................................................................................................ 32
Future Directions ............................................................................................................... 33
References .......................................................................................................................... 34
Figures and Tables

Figure 1 ................................................................................................................. 40

Figure 2 ................................................................................................................. 41

Figure 3 ................................................................................................................. 42
Figure 4 ................................................................................................................. 44

Figure 5 ................................................................................................................. 46

Table 1 .................................................................................................................. 48

Figure 6 ................................................................................................................. 50

Table 2 .................................................................................................................. 52

Figure 7 ................................................................................................................. 54

Table 3 .................................................................................................................. 56

Figure 8 ................................................................................................................. 58

Figure 9 ................................................................................................................. 61

Table 4 .................................................................................................................. 65

Figure 10 ............................................................................................................... 66

Figure 11 ............................................................................................................... 69

Figure 12 ............................................................................................................... 73



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