Prostaglandin E2 exerts the proapoptotic and antiproliferative effects on bovine NK cells

The aim of this research was to determine whether prostaglandin Ey (PGE(2)) affects bovine NK cells in respect of their counts, apoptosis and proliferation, and if it does, then which of the PGE(2) receptor (EP) subtype(s) mediate(s) these effects. We here report that long-term, but not short-term, exposure of bovine peripheral blood mononuclear cells to PGE(2) at 10(-5) M, 10(-6) M and 10(-7) M, but not at 10(-8) M, caused a significant increase in the percentage of early apoptotic cells among NK cell subset. Moreover, PGE(2) at 10(-5) M and 10(-6) M, but not at 10(-7) M and 10(-8) M, induced a considerable decrease in the absolute count of NK cells. The magnitude of these effects increased with an increasing concentration of PGE(2). The blockade of EP1, EP2, EP3 and EP4 receptors did not prevent the PGE(2)-induced apoptosis and depletion of NK cells. The results suggest that the proapoptotic effect of PGE(2) is secondary in character and the induction of this effect is not mediated through EP receptors. Furthermore, the studies demonstrated that PGE(2) at 10(-5) M and 10(-6) M, but not at 10(-7)M and 10(-8) M, highly significantly reduced the percentage of proliferating NK cells. The EP1, EP1/2 and EP3 receptor antagonists were unable to block this effect significantly, whereas the selective blockade of EP4 receptors prevented the PGE(2)-induced inhibition of NK cells proliferation. These results indicate that PGE(2) at certain concentrations may impair the proliferation of NK cells and this effect is mediated via the EP4 receptor. (C) 2016 Elsevier Ltd. All rights reserved.