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 previously 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 placenta has not yet been specified. IL-15 influences cell adhesion and migration 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 investigated the effect of IL-15 (concentrations, 1-10 ng/ml) in a trophoblast invasion model (JEG-3 with matrigel-coated filters). Cell invasion was assessed using matrigel-coated filters and was expressed as the quotient of invading cells in comparison with the number of cells that had passed the control membrane. Cell migration was studied by examining the number of cells that had passed the filters without matrigel. Cell proliferation was quantified 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 fourfold increase in the invasion at a concentration of 10 ng/ml of IL-15. Migration also was increased by a factor of 2.3 (P < 0.05). Cell proliferation, however, remained unchanged. The collagenolytic activity of cytotrophoblastic (JEG-3) cells was increased by IL-15 stimulation. A significant increase 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 metalloproteinase-1 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 might be related to the changes of cell adhesion molecule phenotype during the process of invasion.