Ovine trophoblast protein-1 and human interferon alpha reduce prostaglandin synthesis by ovine endometrial cells.
Ovine trophoblast protein-1 (oTP-1), a protein secreted by the sheep conceptus immediately prior to implantation has sequence homology with alpha interferon. We have previously shown that, in parallel with human alpha interferon (IFN), oTP-1 reduces the release of prostaglandins (PG) E and F2 alpha from cultured ovine endometrial cells. Here we have examined the time and dose dependence of these actions and the possible site of action of the peptides. The concentrations of oTP-1 and IFN required for 50% inhibition of PGE release were 92 pg/ml and 0.88 pg/ml and for PGF2 alpha release, 165 pg/ml and 1.12 pg/ml respectively. Significant effects on PG release were not measured before 12 h after addition of peptide to culture dishes. Following removal of the peptides, the cells released less PGs for a further 18 h but then recovered. A large increase in PG synthesis and release occurred from cells cultured with added serum or arachidonic acid (AA) and an interactive effect was demonstrated between them, AA having a greater stimulatory effect on PG released in the presence of serum. However, in all cases oTP-1 and IFN continued to attenuate prostaglandin release. We conclude that the IFNs act directly or indirectly on the prostaglandin synthase enzyme.
Salamonsen
L A
LA
Medical Research Center, Monash Medical Center, Prince Henry's Hospital, Melbourne, Australia.
Manikhot
J
J
Healy
D L
DL
Findlay
J K
JK
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D001769:Blood; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007700:Kinetics; D050356:Lipid Metabolism; D011257:Pregnancy Proteins / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D012756:Sheep
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D007370:Interferon Type I; D011257:Pregnancy Proteins; D011453:Prostaglandins; C020947:interferon tau