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1 Department of Thoracic Medicine, National Heart & Lung Institute Imperial College London, London, United Kingdom
* To whom correspondence should be addressed. E-mail: l.donnelly{at}imperial.ac.uk.
Resveratrol (3,4',5-trihydroxystilbene) is a polyphenolic stilbene found in the skins of red fruits including grapes that may be responsible for some of the health benefits ascribed to the consumption of red wine. Resveratrol has
previously been shown to have anti-oxidant properties and can act as an estrogen agonist. This study examined the anti-inflammatory effects of resveratrol on human airway epithelial cells. Resveratrol and the related molecule quercetin, but not deoxyrhapontin, inhibited both interleukin (IL)-8 and granulocyte-macrophage colony stimulating factor (GM-CSF) release from A549 cells. Neither the estrogen receptor antagonist, tamoxifen, nor the
glucocorticoid antagonist, mifepristone, altered the inhibitory effect of resveratrol. The mechanism of resveratrol action was investigated further using luciferase reporter genes stably transfected into A549 cells. Both resveratrol and quercetin inhibited NF-
B-, AP-1- and CREB-dependent transcription to a greater extent than the glucocorticosteroid, dexamethasone.
These compounds also had no significant effect on acetylation or deacetylation of core histones. Resveratrol, but not estradiol or N-acetyl cysteine, inhibited cytokine-stimulated inducible nitric oxide synthase
expression and nitrite production (IC50 3.6±2.9 µM) in human primary airway
epithelial cells. Resveratrol also inhibited GM-CSF release (IC50 0.44±0.17µM), IL-8 release (IC50 4.7±3.3µM) and cyclo-oxygenase-2 expression in these cells. This study demonstrates that resveratrol and quercetin have novel non-steroidal anti-inflammatory activity that may have
applications for the treatment of inflammatory diseases.
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