Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 287; no. 4; pp. L774 - L783
• Main Authors: Donnelly, Louise E, Newton, Robert, Kennedy, Gina E, Fenwick, Peter S, Leung, Rachel H. F, Ito, Kazuhiro, Russell, Richard E. K, Barnes, Peter J
• Format: Journal Article
• Language: English
• Published: United States 01.10.2004
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Cell Culture Techniques - methods; Cell Line; Dexamethasone - pharmacology; Granulocyte-Macrophage Colony-Stimulating Factor - secretion; Inflammation - prevention & control; Kinetics; Lung; Quercetin - pharmacology; Respiratory Mucosa - drug effects; Respiratory Mucosa - physiology; Stilbenes - pharmacology; Transfection
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00110.2004

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 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 consumption of red wine. Resveratrol has been shown to have antioxidant 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 IL-8 and granulocyte-macrophage colony-stimulating factor 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. Resveratrol and quercetin inhibited NF- B-, activator protein-1-, and cAMP response element binding protein-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 (IC 50 = 3.6 ± 2.9 µM) in human primary airway epithelial cells. Resveratrol also inhibited granulocyte-macrophage colony-stimulating factor release (IC 50 = 0.44 ± 0.17 µM), IL-8 release (IC 50 = 4.7 ± 3.3 µM), and cyclooxygenase-2 expression in these cells. This study demonstrates that resveratrol and quercetin have novel nonsteroidal anti-inflammatory activity that may have applications for the treatment of inflammatory diseases. inducible nitric oxide synthase; quercetin; red wine 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{at}imperial.ac.uk )