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

Abstract

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-kappaB-, 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 (IC50 = 3.6 +/- 2.9 microM) in human primary airway epithelial cells. Resveratrol also inhibited granulocyte-macrophage colony-stimulating factor release (IC50 = 0.44 +/- 0.17 microM), IL-8 release (IC50 = 4.7 +/- 3.3 microM), 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.

Dietary factors and lung function in the general population: wine and resveratrol intake

“…A putative candidate that may account for the observed beneficial effect of wine is resveratrol, a polyphenol present in the skin of grapes. Resveratrol possesses antiinflammatory properties in airway epithelial cells [10] and alveolar macrophages derived from COPD patients [11]. The mechanism of this action may be explained by the resveratrol-mediated induction of Sirtuin (SIRT)1 activity [12,13].…”

Anti-atherogenic effects of resveratrol

“…Both in vivo and in vitro anti-inflammatory effects of RS and the underlying mechanism have been suggested (Udenigwe et al, 2008). RS inhibits the activity of cyclooxygenase-2, which is the enzyme producing PGE2, a vital component to mediate inflammation (Donnelly et al, 2004). Interleukin-6 has been implicated as an important marker in the process of inflammation and the progression of atherosclerotic plaques .…”

“…Cultured murine macrophages, after treatment with RS, have been shown to reduce gene expression, synthesis and secretion of interleukin-6 (Zhong et al, 1999). The inflammatory process was found to be suppressed by RS, through mediating various inflammatory markers such as inhibition of secretion of interleukin-8 and granulocyte macrophage colony-stimulating factors (Culpitt et al, 2003;Donnelly et al, 2004), endothelial-leukocyte adhesion molecules, vascular cell adhesion molecule-1, and by inhibiting the secretion of histamine and tumor necrosis factor-a (Carluccio et al, 2003).…”

Resveratrol: A miraculous natural compound for diseases treatment

“…RSV causes human platelets aggregation in vitro (Bertelli et al., 1996), therefore recommended not to intake with anticoagulants and antiplatelet drugs (Abu‐Amero, Kondkar, & Chalam, 2016). Nowadays, RSV attracts increasing attention due to naturally occurring compound and the wide range of biological activity and preventive effects on different diseases such as cancers (Gusman, Malonne, & Atassi, 2001; Savouret & Quesne, 2002), neurodegenerative diseases (Chang et al., 2012), cardiovascular disease (Cao & Li, 2004), anti‐inflammatory (Donnelly et al., 2004; Koushki, Dashatan, & Meshkani, 2018), and antioxidant activities (Kawada, Seki, Inoue, & Kuroki, 1998). In addition to RSV, different oligomers (Lins, Ribeiro, Gottlieb, & Gottlieb, 1982) of this compound were found to exhibit broadly biological activities, such as antiviral, anti‐fungal, antibacterial, and anticancer activities (Li, Henry, & Seeram, 2009; Zain, Ahmat, Norizan, & Nazri, 2011).…”