Resveratrol has salutary effects on mucociliary transport and inflammation in sinonasal epithelium

Authors

  • Nathan S. Alexander MD,

    1. Department of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
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  • Neal Hatch BS,

    1. Department of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
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  • Shaoyan Zhang PhD,

    1. Department of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
    2. Gregory Fleming James Cystic Fibrosis Research Center, and University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
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  • Daniel Skinner BS,

    1. Gregory Fleming James Cystic Fibrosis Research Center, and University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
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  • James Fortenberry BS,

    1. Gregory Fleming James Cystic Fibrosis Research Center, and University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
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  • Eric J. Sorscher MD,

    1. Gregory Fleming James Cystic Fibrosis Research Center, and University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
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    • This research was funded by the American Rhinologic Society New Investigator Award (2009) and Flight Attendant's Medical Research Institute Young Clinical Scientist Award (072218) to B.A.W., and NIH/NIDDK (5P30DK072482-03) to E.J.S.

    • Dr. Sorscher and Dr. Woodworth are inventors on a patent submitted regarding the possible activity of chloride secretagogues for therapy of sinus disease (Provisional Patent Application Under 35 U.S.C. §111(b) and 37 C.F.R. §1.53(c) in the United States Patent and Trademark Office). Dr. Woodworth is a consultant for Gyrus ENT, ArthroCare ENT, and was on the GlaxcoSmithKline speaker's bureau.

  • Bradford A. Woodworth MD

    Corresponding author
    1. Department of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
    2. Gregory Fleming James Cystic Fibrosis Research Center, and University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
    • Department of Surgery, University of Alabama at Birmingham, BDB 563, 1530 3rd Ave. S., Birmingham, AL 35294
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    • Dr. Sorscher and Dr. Woodworth are inventors on a patent submitted regarding the possible activity of chloride secretagogues for therapy of sinus disease (Provisional Patent Application Under 35 U.S.C. §111(b) and 37 C.F.R. §1.53(c) in the United States Patent and Trademark Office). Dr. Woodworth is a consultant for Gyrus ENT, ArthroCare ENT, and was on the GlaxcoSmithKline speaker's bureau.


  • This work was presented at the Triological Society's Combined Section meeting, Scottsdale, AZ, January 30, 2011.

Abstract

Objective/Hypothesis:

Therapeutic agents that enhance mucociliary transport (via stimulation of transepithelial Cl secretion) and inhibit inflammation could provide considerable advantages over conventional treatments for chronic rhinosinusitis (CRS). The objectives of the present study were to investigate whether the polyphenolic compound resveratrol promotes transepithelial Cl transport and inhibits KC/IL-8 secretion in sinonasal epithelium.

Study Design:

In vitro and in vivo study.

Methods:

Transepithelial Cl transport was investigated in primary murine nasal septal (MNSE) and human sinonasal epithelial (HSNE) cultures. In vivo activity was also measured using the murine nasal potential difference assay. CFTR R-domain phosphorylation and cAMP levels were examined as a test of cAMP/PKA-dependent activation. In vitro LPS-induced KC/IL-8 secretion was quantified and compared to a panel of intranasal steroids.

Results:

Resveratrol(100 μM) significantly increased CFTR-mediated Cl transport (change in short-circuit current, ΔISC) in both MNSE (13.51 ± 0.77 vs. 4.4 ± 0.66 [control]; P < .05) and HSNE (12.28 ± 1.08 vs. 0.69 ± 0.32 [control]; P < .05). Cl secretion across in vivo murine nasal epithelium was also enhanced (−4 ± 1.8 vs. −0.8 ± 1.7mV [control], P < .05). There was no increase in cellular cAMP or CFTR R-domain phosphorylation detected. Resveratrol also significantly inhibited KC/IL-8 secretion in a dose-dependent fashion (pg/mL) in MNSE (181 ± 39[100 μM) vs. 94 ± 16 [200 μM] vs. 16 ± 22 [500 μM] vs. 1195 ± 355 [LPS control]; P < .001). The compound robustly abrogated KC/IL-8 secretion when compared to ciclesonide (765 ± 139), triamcinolone (561 ± 124), and budesonide (742 ± 428), but had similar activity to fluticasone proprionate (65 ± 47). Similar effects were demonstrated in HSNE (975 ± 244 [100 μM] vs. 1825 ± 144 [LPS control]; P < .001) with inhibition comparable to fluticasone proprionate (785 ± 277).

Conclusions:

These in vitro and in vivo findings indicate resveratrol is a potent Cl secretagogue and anti-inflammatory agent. Future clinical trials for CRS are warranted.

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