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Anti-inflammatory Effects of Resveratrol in Lung Epithelial Cells: Molecular Mechanisms
</NOBR><NOBR>Louise E. Donnelly,<SUP></SUP></NOBR> <NOBR>Robert Newton,<SUP></SUP></NOBR> <NOBR>Gina E. Kennedy,<SUP></SUP></NOBR> <NOBR>Peter S. Fenwick,<SUP></SUP></NOBR> <NOBR>Rachel H. F. Leung,<SUP></SUP></NOBR> <NOBR>Kazuhiro Ito,<SUP></SUP></NOBR> <NOBR>Richard E. K. Russell,<SUP></SUP></NOBR> and <NOBR>Peter J. Barnes<SUP></SUP></NOBR>
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, London SW3 6LY, United Kingdom
Submitted 8 January 2004 ; accepted in final form 22 May 2004
<!-- ABS -->Resveratrol (3,4',5-trihydroxystilbene) is a polyphenolic stilbene<SUP> </SUP>found in the skins of red fruits, including grapes, that may<SUP> </SUP>be responsible for some of the health benefits ascribed to consumption<SUP> </SUP>of red wine. Resveratrol has been shown to have antioxidant<SUP> </SUP>properties and can act as an estrogen agonist. This study examined<SUP> </SUP>the anti-inflammatory effects of resveratrol on human airway<SUP> </SUP>epithelial cells. Resveratrol and the related molecule quercetin,<SUP> </SUP>but not deoxyrhapontin, inhibited IL-8 and granulocyte-macrophage<SUP> </SUP>colony-stimulating factor release from A549 cells. Neither the<SUP> </SUP>estrogen receptor antagonist tamoxifen nor the glucocorticoid<SUP> </SUP>antagonist mifepristone altered the inhibitory effect of resveratrol.<SUP> </SUP>The mechanism of resveratrol action was investigated further<SUP> </SUP>using luciferase reporter genes stably transfected into A549<SUP> </SUP>cells. Resveratrol and quercetin inhibited NF-
B-, activator<SUP> </SUP>protein-1-, and cAMP response element binding protein-dependent<SUP> </SUP>transcription to a greater extent than the glucocorticosteroid<SUP> </SUP>dexamethasone. These compounds also had no significant effect<SUP> </SUP>on acetylation or deacetylation of core histones. Resveratrol,<SUP> </SUP>but not estradiol or N-acetyl cysteine, inhibited cytokine-stimulated<SUP> </SUP>inducible nitric oxide synthase expression and nitrite production<SUP> </SUP>(IC<SUB>50</SUB> = 3.6 ? 2.9 ?M) in human primary airway epithelial<SUP> </SUP>cells. Resveratrol also inhibited granulocyte-macrophage colony-stimulating<SUP> </SUP>factor release (IC<SUB>50</SUB> = 0.44 ? 0.17 ?M), IL-8 release<SUP> </SUP>(IC<SUB>50</SUB> = 4.7 ? 3.3 ?M), and cyclooxygenase-2 expression<SUP> </SUP>in these cells. This study demonstrates that resveratrol and<SUP> </SUP>quercetin have novel nonsteroidal anti-inflammatory activity<SUP> </SUP>that may have applications for the treatment of inflammatory<SUP> </SUP>diseases.<SUP> </SUP>
inducible nitric oxide synthase; quercetin; red wine
<HR align=left width="50%" noShade SIZE=1><!-- null -->
Address for reprint requests and other correspondence: L. E. Donnelly, Dept. of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse St., London SW3 6LY, UK (E-mail: l.donnelly@imperial.ac.uk<SCRIPT type=text/javascript><!-- var u = "l.donnelly", d = "imperial.ac.uk"; document.getElementById("em0").innerHTML = '<a href="mailto:' + u + '@' + d + '">' + u + '@' + d + '<\/a>'//--></SCRIPT> )
Am J Physiol Lung Cell Mol Physiol 287: L774-L783, 2004. First published June 4, 2004; doi:10.1152/ajplung.00110.2004
1040-0605/04 $5.00
full text at: http://ajplung.physiology.org/cgi/content/full/287/4/L774
hat-tip to ecojosh!
</NOBR><NOBR>Louise E. Donnelly,<SUP></SUP></NOBR> <NOBR>Robert Newton,<SUP></SUP></NOBR> <NOBR>Gina E. Kennedy,<SUP></SUP></NOBR> <NOBR>Peter S. Fenwick,<SUP></SUP></NOBR> <NOBR>Rachel H. F. Leung,<SUP></SUP></NOBR> <NOBR>Kazuhiro Ito,<SUP></SUP></NOBR> <NOBR>Richard E. K. Russell,<SUP></SUP></NOBR> and <NOBR>Peter J. Barnes<SUP></SUP></NOBR>
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, London SW3 6LY, United Kingdom
Submitted 8 January 2004 ; accepted in final form 22 May 2004
<!-- ABS -->Resveratrol (3,4',5-trihydroxystilbene) is a polyphenolic stilbene<SUP> </SUP>found in the skins of red fruits, including grapes, that may<SUP> </SUP>be responsible for some of the health benefits ascribed to consumption<SUP> </SUP>of red wine. Resveratrol has been shown to have antioxidant<SUP> </SUP>properties and can act as an estrogen agonist. This study examined<SUP> </SUP>the anti-inflammatory effects of resveratrol on human airway<SUP> </SUP>epithelial cells. Resveratrol and the related molecule quercetin,<SUP> </SUP>but not deoxyrhapontin, inhibited IL-8 and granulocyte-macrophage<SUP> </SUP>colony-stimulating factor release from A549 cells. Neither the<SUP> </SUP>estrogen receptor antagonist tamoxifen nor the glucocorticoid<SUP> </SUP>antagonist mifepristone altered the inhibitory effect of resveratrol.<SUP> </SUP>The mechanism of resveratrol action was investigated further<SUP> </SUP>using luciferase reporter genes stably transfected into A549<SUP> </SUP>cells. Resveratrol and quercetin inhibited NF-
inducible nitric oxide synthase; quercetin; red wine
<HR align=left width="50%" noShade SIZE=1><!-- null -->
Address for reprint requests and other correspondence: L. E. Donnelly, Dept. of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse St., London SW3 6LY, UK (E-mail: l.donnelly@imperial.ac.uk<SCRIPT type=text/javascript><!-- var u = "l.donnelly", d = "imperial.ac.uk"; document.getElementById("em0").innerHTML = '<a href="mailto:' + u + '@' + d + '">' + u + '@' + d + '<\/a>'//--></SCRIPT> )
Am J Physiol Lung Cell Mol Physiol 287: L774-L783, 2004. First published June 4, 2004; doi:10.1152/ajplung.00110.2004
1040-0605/04 $5.00
full text at: http://ajplung.physiology.org/cgi/content/full/287/4/L774
hat-tip to ecojosh!