Biological Activities of a Human Amniotic Membrane Interferon

Abstract

In order to characterize further the human amniotic membrane interferon (IFN-AM), an interferon antigenically unrelated to human IFN-α, -β, and -γ or TNF, we analysed its biological activities. Here, we present direct evidence of its ability to affect cell growth and to induce the IFN-stimulated genes (ISGs) 6–16 and 2′–5′ oligoadenylate synthetase (OAS), in addition to its crossed anti-viral activity. The cellular growth arrest effect of IFN-AM was dose-dependent and paralleled that of IFN-β. IFN-AM was also able to inhibit thymidine incorporation into DNA, similar to IFN-β. The mRNA induction of 6–16 gene with IFN-AM treatment reached its highest level at 500IU/ml and remained constant up to 2000IU/ml. Conversely, 2′–5′ OAS mRNA induction was dose-dependent, with the maximum level detected at 2000IU/ml of IFN-AM treatment. The time course of mRNA accumulation by ISGs with IFN-AM (500IU/ml) stimulation was also investigated. Gene induction reached a maximum at 16h after IFN treatment for 2′–5′ OAS and at 48h for the 6–16 gene. IFN-AM and human IFN-α induced similar levels of the OAS enzyme. IFN-AM also showed small but significant activity in bovine cells.In conclusion, the amniotic membrane IFN here studied showed both anti-cellular activity and the ability to stimulate ISG-transcriptional activation in a similar manner to IFN-β. In addition, IFN-AM was also as able to induce the expression of the enzyme 2′–5′ OAS, as did IFN-α. Lastly, amniotic IFN showed a significant cross-species anti-viral activity, which was different from both human IFN-α and -β. Taken together, these data strongly suggest that IFN-AM is a novel sub-type I IFN.