Fig. 3

Resveratrol modulates the NKG2D receptor/NKG2D-L system by increasing expression in NK cells and in transformed target cells. Enhanced expression of NKG2D receptor and cytotoxins in NK cells together with upregulation of NKG2D ligands and DRs on target cell surface lead to enhanced killing efficacy. NK cells use two different mechanisms to kill the targets: i) by cytotoxic granule exocytosis ii) by induction of death receptor-mediated apoptosis. Increased IFN-γ production by resveratrol enhances TRAIL expression, which can facilitate apoptosis induction. Inhibitory signalling is often too weak to prevent NK cell killing due to downregulated expression of MHC I proteins in virus-infected or malignantly transformed cells. Further activating signals can provide NCR ligands of different origin. DR4/5, death receptor 4/5; MHC I, major histocompatibility complex I; MICA/B, MHC class I-related chain A/B; NK cells, natural killer cells; NKG2D, natural-killer group 2, member D; NKp30/44, natural killer cell p30/44-related protein; TRAIL, TNF-related apoptosis-inducing ligand; ULBP1-3, UL16 binding protein 1–3