PROBLEM: Trophoblast invasion into the uterus is controlled by many factors
. Some cytokines (interleukin [IL]-1, IL-6, and IL-10) have been shown prev
iously to play an important role in placentation. The human placenta is an
important source of IL-15, although the cellular source of IL-15 in the pla
centa has not yet been specified. IL-15 influences cell adhesion and migrat
ion by redistributing adhesion molecules in lymphocytes and has been shown
to have effects on endothelial cells and in some human tumors.
METHOD OF STUDY: To study the role of IL-15 in trophoblast invasion, we inv
estigated the effect of IL-15 (concentrations, 1-10 ng/ml) in a trophoblast
invasion model (JEG-3 with matrigel-coated filters). Cell invasion was ass
essed using matrigel-coated filters and was expressed as the quotient of in
vading cells in comparison with the number of cells that had passed the con
trol membrane. Cell migration was studied by examining the number of cells
that had passed the filters without matrigel. Cell proliferation was quanti
fied by a tetrazolium salt WST-1 cleavage assay. Matrix metalloproteinase (
MMP)-1, MMP-2, and MMP-9 activities were measured by specific enzyme assays
.
RESULTS: IL-15 significantly (P < 0.05) increased the in vitro invasion of
cytotrophoblastic (JEG-3) cells in a dose-dependent manner. There was a fou
rfold increase in the invasion at a concentration of 10 ng/ml of IL-15. Mig
ration also was increased by a factor of 2.3 (P < 0.05). Cell proliferation
, however, remained unchanged. The collagenolytic activity of cytotrophobla
stic (JEG-3) cells was increased by IL-15 stimulation. A significant increa
se in MMP-1 concentration occurred after the incubation of JEG-3 cells with
IL-15. No changes appeared in MMP-2, MMP-9, and tissue inhibitor of metall
oproteinase-l concentrations.
CONCLUSIONS: Trophoblast invasion and migration, but not proliferation, are
enhanced by IL-15. Our results suggest a role for IL-15 in the modulation
of MMP-1 secretion by JEG-3 cells. Furthermore, we speculate, that IL-15 mi
ght be related to the changes of cell adhesion molecule phenotype during th
e process of invasion.