Resveratrol differentially modulates immune responses in human THP-1 monocytes and macrophages

Resveratrol (Res), a natural polyphenol compound found in grapes and red wine, has been shown to exhibit anti-inflammatory, antioxidant, and anticarcinogenic effects. However, proinflammatory/tumor-promoting properties of Res have also been reported, rendering the polyphenol's reported therapeutic benefits less convincing and controversial. To evaluate the underlying plausible factors contributing to the differential immunomodulatory effects imparted by Res, herein, we investigated, at both physiological and pharmacological doses, the in vitro effects of Res on cell survival/proliferation, inflammatory genes, and cytokine production in human monocytic cell line (THP-1) and phorbol 12-myristate 13-acetate differentiated human THP-1-derived macrophages. We hypothesized that the differential effects observed in monocytes and macrophages may largely depend on dietary vs pharmacological doses of Res, duration of treatment, and the target cells it acts upon. Our data showed that Res, at physiological concentrations, inhibited proliferation of THP-1 monocytes with S phase arrest. On the other hand, at pharmacological concentrations, Res induced cell apoptosis and caused G0/G1 phase arrest. Additionally, Res showed differential effects on proinflammatory cytokine expression and production measured by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively, in THP-1 monocytes vs macrophages: promoting inflammation in monocytes while exhibiting anti-inflammatory effects in macrophages. Comparative analysis on Res and 2 other phytochemicals, pterostilbene and genistein, revealed that the immunomodulatory effects of Res were consistent with those observed in pterostilbene and not genistein. Our results reveal a pleiotropic immunomodulatory property of Res that is dose-time-target cell-dependent and thus serve as a caution for the use of Res in the treatment of inflammatory diseases.