title: Control of eotaxin-1 expression and release by resveratrol and its metabolites in culture human pulmonary artery endothelial cells.
abstract: Population studies suggest that moderate red wine intake correlates with reduced risk of cardiovascular disease (CVD); cardioprotection may attribute to consumption of red wine polyphenol resveratrol. Since inflammation plays a key role in CVD, we investigated modulation of inflammation by resveratrol and its metabolites by determining the expression and release of chemokine, eotaxin-1, in cultured human pulmonary artery endothelial cells (HPAEC) treated with proinflammatory cytokines IL-13 and TNF-α. Up-regulation of eotaxin-1 gene expression by IL-13 or TNF-α was confirmed by RT-PCR, by reporter assays using eotaxin-1 gene promoter constructs, and by the changes in transcriptional factors STAT6 and NF-κB. Exposure to resveratrol suppressed IL-13 and TNF-α induced eotaxin-1 gene expression as well as attenuated the eotaxin-1 promoter activity, in coordination with inhibition of expression of JAK-1, reduction in phosphorylated-STAT6 and decreased p65 subunit of NF-κB. In addition, quantitative determination of eotaxin-1 release using enzyme-linked immunosorbent assay (ELISA) showed increased eotaxin-1 release in response to treatment by IL-13 and TNF-α, which was effectively inhibited by resveratrol. Whether resveratrol metabolites affected eotaxin-1 was also tested; piceatannol showed potency similar to resveratrol. We propose that control of eotaxin-1 expression and release by proinflammatory cytokines in HPAEC may be considered as an in vitro model for screening and discovering polyphenols with anti-inflammatory activities and cardioprotective potentials.
authors.affiliation: Department of Biochemistry & Molecular Biology, New York Medical College Valhalla, New York 10595, USA.
authors.forename: Ching Jen
authors.initials: CJ
authors.lastname: Yang
authors.forename: Chia Yi
authors.initials: CY
authors.lastname: Lin
authors.forename: Tze-Chen
authors.initials: TC
authors.lastname: Hsieh
authors.forename: Susan C
authors.initials: SC
authors.lastname: Olson
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Wu