Invasion of cytotrophoblastic (JEG-3) cells is up-regulated by interleukin-15 in vitro

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.