Basal and interferon-induced 2',5'-oligoadenylate synthetase activity in human placental trophoblast and trophoblast-derived malignant cell lines.
Human placental trophoblasts produce interferon (tro-IFNs) when stimulated with viral inducers. Since the antiviral and cellular functions of IFNs are partly mediated by the 2',5'-oligoadenylate synthetase (2-5A synthetase) pathway, the aim of the present study was to determine the basal and IFN-induced levels of 2-5A synthetase in villous trophoblast cultures. A considerable basal level of 2-5A synthetase was observed 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 (Far, FEG-3, and BeWo). Stimulation with tro-IFN-beta, -alpha and leucocyte-IFN (leu-IFN)-alpha increased the enzyme activity in first and third trimester human syncytiotrophoblast cultures. Treatment with recombinant-IFN (rec-IFN)-gamma significantly enhanced 2-5A synthetase activity in first trimester syncytiotrophoblast, but had no effect on third trimester syncytiotrophoblast. Tro-IFN-beta, -alpha and leu-IFN-alpha induced high levels of 2-5A synthetase activity in placental fibroblast, BeWo and FEG-3 cell-lines, whereas rec-IFN-gamma treatment did not induce 2-5A synthetase activity in any of these cells. No detectable 2-5A synthetase activity was found in the Far cell line. The capability of cells deriving from the fetoplacental unit to raise an antiviral response by the induction of 2-5A synthetase may be important in defending the fetus against viral infection from the mother. Furthermore 2-5A synthetase in cells of the fetoplacental unit may play a role in their normal growth and development.
Dalsgaard
A M
AM
Department of Virus and Cancer, Danish Cancer Society, Aarhus.
Aboagye-Mathiesen
G
G
Justesen
J
J
Zdravkovic
M
M
Ebbesen
P
P
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis*; D001481:Basal Metabolism; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000201:enzymology*; D011261:Pregnancy Trimester, First; D011263:Pregnancy Trimester, Third; D012016:Reference Values; D014328:Trophoblastic Neoplasms / Q000201:enzymology*; D014327:Trophoblasts / Q000201:enzymology*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000201:enzymology*
D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase