THE EFFECTS OF CYTOKINES ON HUMAN CHORIONIC-GONADOTROPIN (HCG) PRODUCTION BY A TROPHOBLAST CELL-LINE

The present study was conducted to investigate the effects of cytokines on human chorionic gonadotropin (hCG) and its alpha- and beta-subunit release as well as protein synthesis in a trophoblast cell line. The human choriocarcinoma cell line, Jar, was used as a trophoblast model. Jar cells were incubated for 24 h with varying concentrations(5 x 10(-4)-40 mu g/ml) of the following cytokines: Il-1, Il-2, Il-3, Il-4, Il-5, Il-6, IFN-gamma, tumor necrosis factor (TNF)-alpha, M-CSF and GM-CSF. Supernatants were assayed for hCG and its alpha- and beta-subunits by immunoradiometric methods. Cytotoxic effects were assessed by trypan blue staining. Protein synthesis was measured by [H-3]leucine incorporation. The cytokines Il-1 and TNF-alpha significantly stimulated hCG release. The other cytokines had no significant effect on hCG production. Protein synthesis by the Jar cells was not significantly affected by either IL-1 or TNF-alpha. However, IFN-gamma (40 mu g/ml) significantly suppressed protein synthesis by the Jar cells. Trophoblast viability in the presence of TNF-alpha (10 mu g/ml) and IFN-gamma (40 mu g/ml) was only 40% and 50%, respectively. These results suggest that cytokines may be important regulators of trophoblast function. Il-1 appears to have a stimulatory effect on trophoblast hCG release, while TNF-alpha and IFN-gamma appear to have cytotoxic effects on trophoblast cells.