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

Abstract The aim of this research was to determine whether prostaglandin E 2 (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.