Biological activities of a human amniotic membrane interferon.
In order to characterize further the human amniotic membrane interferon (IFN-AM), an interferon antigenically unrelated to human IFN-alpha, -beta, and -gamma 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-beta. IFN-AM was also able to inhibit thymidine incorporation into DNA, similar to IFN-beta. The mRNA induction of 6-16 gene with IFN-AM treatment reached its highest level at 500 IU/ml and remained constant up to 2000 IU/ml. Conversely, 2'-5' OAS mRNA induction was dose-dependent, with the maximum level detected at 2000 IU/ml of IFN-AM treatment. The time course of mRNA accumulation by ISGs with IFN-AM (500 IU/ml) stimulation was also investigated. Gene induction reached a maximum at 16 h after IFN treatment for 2'-5' OAS and at 48 h for the 6-16 gene. IFN-AM and human IFN-alpha 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-beta. In addition, IFN-AM was also as able to induce the expression of the enzyme 2'-5' OAS, as did IFN-alpha. Lastly, amniotic IFN showed a significant cross-species anti-viral activity, which was different from both human IFN-alpha and -beta. Taken together, these data strongly suggest that IFN-AM is a novel sub-type I IFN.
Franco
G R
GR
Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
de Carvalho
A F
AF
Kroon
E G
EG
Lovagie
S
S
Werenne
J
J
Golgher
R R
RR
Ferreira
P C
PC
Bonjardim
C A
CA
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D000650:Amnion / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D002455:Cell Division; D002460:Cell Line; D002522:Chlorocebus aethiops; D004247:DNA / Q000096:biosynthesis; D004285:Dogs; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D007668:Kidney; D012333:RNA, Messenger; D013045:Species Specificity; D014407:Tumor Cells, Cultured; D014709:Vero Cells
D016898:Interferon-alpha; D012333:RNA, Messenger; D004247:DNA; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase