Expression of prolactin receptor and response to prolactin stimulation of human NK cell lines

We have previously shown a critical role of prolactin (PRL) during maturation and anti-tumor effects of murine natural killer (NK) cells in vitro and in vivo. We extended that study by exploring the ability of human NK cell lines (NK-92 and YT cell) to express PRL receptor (PRL-R) and to respond to PRL stimulation in vitro. Both human NK cell lines constitutively expressed PRL-R on membrane and mRNA transcripts, NK-92 cells contained higher level of PRL-R than YT cells, which con-elated to the enhanced capacity of the cells to proliferate and to lyse target cells in response to PRL Stimulation in the presence of trace amount of IL-2 or IL-15 in vitro. Two differences between IL-2 and IL-15 in functioning on human NK cells were for the first time observed. PRL synergized with IL-15 to improve proliferation of NK cells in a dose-dependent manner without double peak manifesting like IL-2. Although PRL enhanced the cytotoxicity of IL-2 or IL-15 activated NK cells, it exerted the function through up-regulating gene expression of perforin without influence of FasL in IL-2-stimulated NK cells, while in IL-15-stimulated NK cells, PRL did the function through up-regulating gene expression of both perforin and FasL but not IFNgamma. PRL increased expressions of IL-2Ralpha on membrane and of IL-2 rnRNA in cells, indicating that PRL up-reoulated NK cell function by improving positive feed-back between IL-2 and IL-2R. The similar results were also observed in network between IL-15 and IL-15R. These data indicate a potential role of PRL in human NK cell modulation.