Resveratrol Attenuates Stimulated T-Cells Activation and Proliferation: A Novel Therapy Against Cellular Rejection in Cardiac Transplantation

Abstract

Purpose Resveratrol is the major bioactive phenol found in red wine and grapes. Resveratrol has been shown to directly inhibit cardiac hypertrophy through inhibition of protein kinase B (PKB/Akt), leading to inhibition of the mammalian target of rapamycin (mTOR). Therefore, we hypothesize that resveratrol can inhibit human T-cell response under stimulation. Methods and Materials Human peripheral blood mononuclear cells (PBMC) were isolated and cultured. The cells were pre-treated with resveratrol (50μM) overnight (18hrs) before stimulation (cell stimulation cocktail – PMA/Ionomycin, eBioscience) for 4 hours. The cells were collected for subsequent biochemical analysis. Cells were stained with proliferation dye and cultured for 5 days in PMA/Ionomycin with resveratrol for flow cytometry analysis. Results In non-stimulated PBMCs, markers of T-cell activation, tumor necrosis factor-α (TNF-α), interferon γ (INF-γ), and cell proliferation were comparable between resveratrol treated cells and controls. However, when PBMCs were stimulated, resveratrol treated cells displayed a significant decrease in TNF-α, INF-γ and cell proliferation, when compared to controls (p Conclusions Taken together, our data suggest that resveratrol is able to decrease the immune response of stimulated T-cells by inhibiting Akt, thus suppressing mTOR mediated cellular signaling. Therefore, resveratrol may be a possible adjunctive therapy for patients undergoing cardiac transplantation, as this drug has a very low side-effect profile, and has pleiotropic effects on decreasing cardiac hypertrophy.