BASAL AND INTERFERON-INDUCED 2',5'-OLIGOADENYLATE SYNTHETASE-ACTIVITYIN HUMAN PLACENTAL TROPHOBLAST AND TROPHOBLAST-DERIVED MALIGNANT-CELLLINES

Human placental trophoblasts produce interferon (tro-IFNs) when stimul ated with viral inducers. Since the antiviral and cellular functions o f IFNs are partly mediated by the 2',5'-oligondenylate synthetase (2-5 A synthetase) pathway, the aim of the present study was to determine t he basal and IFN-induced levels of 2-5A synthetase in villous trophobl ast cultures. A considerable basal level of 2-5A synthetase was observ ed in syncytiotrophoblast cultures from both first and third trimester . In contrast no basal activity was detectable in placental fibroblast and trophoblast- derived malignant cell lines (Jar, JEG-3, and BeWo). Stimulation with tro-IFN-beta, -alpha and leucocyte-IFN (leu-IFN)-alp ha increased the enzyme activity in first and third trimester human sy ncytiotrophoblast cultures. Treatment with recombinant-IFN (rec-IFN)-g amma significantly enhanced 2-5A synthetase activity in first trimeste r syncytiotrophoblast, but had no effect on third trimester syncytiotr ophoblast. Tro-IFN-beta, -alpha and leu-IFN-alpha induced high levels of 2-5A synthetase activity in placental fibroblast, BeWo and JEG-3 ce ll-lines, whereas rec-IFN-gamma treatment did not induce 2-5A syntheta se activity in any of these cells. No detectable 2-5A synthetase activ ity was found in the Jar cell line. The capability of cells deriving f rom the fetoplacental unit to raise an antiviral response by the induc tion of 2-5A synthetase may be important in defending the fetus agains t viral infection from the mother. Furthermore 2-5A synthetase in cell s of the fetoplacental unit may play a role in their normal growth and development.