Differential regulation of the interferon induced gene ISG12A by serum from healthy and preeclamptic pregnancies

Endothelial-cell dysfunction is central in the preeclamptic pathogenesis. Several components present in the blood of the preeclamptic mother are capable of mediating this dysfunction. We analyzed the regulation of the ISG12A gene by serum from the third trimester, to elucidate the role of type 1 interferon ISGs late in both healthy and preeclamptic pregnancies. The ISG12A transcription was up-regulated by serum from healthy pregnant women, but not by preeclamptic serum in HeLa and human umbilical vein endothelial cells (HUVEC). However, the ISG12A up-regulation by healthy pregnancy serum was not due to a general type 1 interferon response, since 6-16 and OAS1 were not up-regulated similarly. Also, the up-regulation of ISG12A was independent of the interferon-alpha receptor 2, but dependent on STAT1. Stimulation with folic acid alone or in combination with preeclamptic serum up-regulated ISG12A and 6-16. We conclude that type 1 interferon is not increased in third trimester serum, neither from healthy nor preeclamptic pregnancies. However, since ISG12A mRNA is up-regulated in healthy pregnancies, the ISG12A protein might take part in maintaining endothelial stability, as this function is lacking in preeclamptic pregnancies. Folic acid may ameliorate endothelial cell stability in preeclampsia by up-regulating ISG12A.