INTERLEUKIN-8 CAN STIMULATE PROGESTERONE SECRETION FROM A HUMAN TROPHOBLAST CELL LINE, BEWO

Abstract

Precise paracrine cross-talk between the embryo and the endometrium is essential for the establishment of a successful pregnancy. Previous studies have demonstrated that the expression of interleukin-8 (IL-8) in the endometrium is enhanced during the late-secretory phase and early pregnancy. Furthermore, IL-8 receptor (IL-8R) expression has been detected in trophoblast cells of the developing embryo. To clarify the roles of IL-8 in the endometrium-embryo interactions, the effects of IL-8 on hormone secretion by trophoblast cells were studied using the BeWo trophoblast cell line that retains hormone-secreting properties of normal trophoblast cells. Using reverse transcription-polymerase chain reaction, we found that IL-8R messenger ribonucleic acid (mRNA) was expressed in BeWo cells. The levels of IL-8R mRNA and protein expression in BeWo cells were similar to those in primary first-trimester trophoblast cells. Progesterone (P4) secretion of BeWo cells was comparable with that of first-trimester trophoblast cells but higher than that of third-trimester trophoblast cells. Treatment of BeWo cells with recombinant human IL-8 (rhIL-8) had no effect on cell proliferation, as determined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Interestingly, secretion of P4, but not human chorionic gonadotropin, from cultured BeWo cells was significantly enhanced when the cells were incubated with rhIL-8. Our results demonstrate that IL-8 may play an important role in the endometrium-embryo interactions by stimulating trophoblast secretion of P4 for maintenance of a successful pregnancy.