Resveratrol Has Salutary Effects on Mucociliary Transport and Inflammation in Sinonasal Epithelium

被引：40

作者：

Alexander, Nathan S. ^{[1
]}

Hatch, Neal ^{[1
]}

Zhang, Shaoyan ^{[1
,2
]}

Skinner, Daniel ^{[1
,2
]}

Fortenberry, James ^{[2
]}

Sorscher, Eric J. ^{[2
]}

Woodworth, Bradford A. ^{[1
,2
]}

机构：

[1] Univ Alabama Birmingham, Dept Surg, Div Otolaryngol, Birmingham, AL 35294 USA

[2] Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL 35294 USA

来源：

LARYNGOSCOPE | 2011年 / 121卷 / 06期

关键词：

Transepithelial ion transport; Resveratrol; CFTR; calcium-activated chloride channel; chronic sinusitis; KC; IL-8; chloride secretion; murine nasal culture; human sinus epithelium; mucociliary clearance; LIQUID INTERFACE CULTURES; TRANSMEMBRANE CONDUCTANCE REGULATOR; CILIARY BEAT FREQUENCY; CYSTIC-FIBROSIS; IN-VITRO; CHRONIC RHINOSINUSITIS; ACTIVATION; CFTR; EXPRESSION; GENISTEIN;

D O I：

10.1002/lary.21798

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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 mu M) significantly increased CFTR-mediated Cl- transport (change in short-circuit current, DISC) 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 mu M) vs. 94 +/- 16 [200 mu M] vs. 16 +/- 22 [500 mu M] vs. 1195 +/- 355 [LPS control]; P < .001). The compound robustly abrogated KC/IL-8 secretion when compared to ciclesonide (765 +/- 139), triamcinolone (561 6 124), and budesonide (742 +/- 428), but had similar activity to fluticasone proprionate (65 +/- 47). Similar effects were demonstrated in HSNE (975 +/- 244 [100 mu M] 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.

引用

页码：1313 / 1319

页数：7

共 30 条

[1] Effect of VX-770 in Persons with Cystic Fibrosis and the G551D-CFTR Mutation [J].

Accurso, Frank J. ;

Rowe, Steven M. ;

Clancy, J. P. ;

Boyle, Michael P. ;

Dunitz, Jordan M. ;

Durie, Peter R. ;

Sagel, Scott D. ;

Hornick, Douglas B. ;

Konstan, Michael W. ;

Donaldson, Scott H. ;

Moss, Richard B. ;

Pilewski, Joseph M. ;

Rubenstein, Ronald C. ;

Uluer, Ahmet Z. ;

Aitken, Moira L. ;

Freedman, Steven D. ;

Rose, Lynn M. ;

Mayer-Hamblett, Nicole ;

Dong, Qunming ;

Zha, Jiuhong ;

Stone, Anne J. ;

Olson, Eric R. ;

Ordonez, Claudia L. ;

Campbell, Preston W. ;

Ashlock, Melissa A. ;

Ramsey, Bonnie W. .

NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (21) :1991-2003

[2] Murine nasal septa for respiratory epithelial air-liquid interface cultures [J].

Antunes, Marcelo B. ;

Woodworth, Bradford A. ;

Bhargave, Geeta ;

Xiong, Guoxiang ;

Aguilar, Jorge L. ;

Ratner, Adam J. ;

Kreindler, James L. ;

Rubenstein, Ronald C. ;

Cohen, Noam A. .

BIOTECHNIQUES, 2007, 43 (02) :195-+

[3] Hesperidin stimulates cystic fibrosis transmembrane conductance regulator-mediated chloride secretion and ciliary beat frequency in sinonasal epithelium [J].

Azbell, Christopher ;

Zhang, Shaoyan ;

Skinner, Daniel ;

Fortenberry, James ;

Sorscher, Eric J. ;

Woodworth, Bradford A. .

OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 2010, 143 (03) :397-404

[4] Transient receptor potential vanilloid type 4 channel expression in chronic rhinosinusitis [J].

Bhargave, Geeta ;

Woodworth, Bradford A. ;

Xiong, Guoxiang ;

Wolfe, Steven G. ;

Antunes, Marcelo B. ;

Cohen, Noarn. A. .

AMERICAN JOURNAL OF RHINOLOGY, 2008, 22 (01) :7-12

[5]

BLACKWELL DL, 2002, VITAL HLTH STAT, V10, P15

[6] Cigarette Smoke Condensate Inhibits Transepithelial Chloride Transport and Ciliary Beat Frequency [J].

Cohen, Noam A. ;

Zhang, Shaoyan ;

Sharp, Dawn B. ;

Tamashiro, Edwin ;

Chen, Bei ;

Sorscher, Eric J. ;

Woodworth, Bradford A. .

LARYNGOSCOPE, 2009, 119 (11) :2269-2274

[7] Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD [J].

Culpitt, SV ;

Rogers, DF ;

Fenwick, PS ;

Shah, P ;

De Matos, C ;

Russell, REK ;

Barnes, PJ ;

Donnelly, LE .

THORAX, 2003, 58 (11) :942-946

[8] Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms [J].

Donnelly, LE ;

Newton, R ;

Kennedy, GE ;

Fenwick, PS ;

Leung, RHF ;

Ito, K ;

Russell, REK ;

Barnes, PJ .

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2004, 287 (04) :L774-L783

[9] AIRWAY NEUTROPHILIA AND CHEMOKINE MESSENGER-RNA EXPRESSION IN SULFUR DIOXIDE-INDUCED BRONCHITIS [J].

FARONE, A ;

HUANG, S ;

PAULAUSKIS, J ;

KOBZIK, L .

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1995, 12 (03) :345-350

[10] Activation of the CFTR Cl- Channel by Trimethoxy-flavone in vitro and in vivo [J].

Fischer, Horst ;

Illek, Beate .

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2008, 22 (5-6) :685-692

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