MODULATION OF PRODUCTION OF MATRIX METALLOPROTEINASES FROM OVINE ENDOMETRIAL CELLS BY OVINE TROPHOBLAST INTERFERON

Ovine trophoblast interferon modulates the secretion of a number of pr oteins by ovine endometrium, but only one of these proteins has so far been identified. We examined the effects of trophoblast interferon on the secretion of matrix metalloproteinase-1, -2 and -3 by cultured ov ine endometrial cells and determined whether they are mediated via eff ects on prostaglandin synthesis. Both ovine trophoblast interferon (30 ng ml(-1)) and human recombinant interferon or (50 U ml(-1)) inhibite d the production of latent matrix metalloproteinase-1 and -3 (P < 0.05 ), as measured by enzyme assays, but had no effect on the secretion of latent matrix metalloproteinase-2. These inhibitory effects were not overcome by PGE(2) or PGF(2 alpha) (each 10 mu mol l(-1)) either alone or in combination. Indomethacin (12 mu mol l(-1)) similarly inhibited the production of latent matrix metalloproteinase-1 and -3, but produ ction was partially restored by adding the prostaglandins either singl y or in combination. PGE(2) and PGF(2 alpha) together had no effect on enzyme production. These data were confirmed by gelatin and casein zy mography. Northern analysis showed a 4.5-fold increase in the abundanc e of specific mRNA for latent matrix metalloproteinase-1 following tre atment of cells with phorbol myristate acetate, but a marked decrease following interferon treatment. Thus, ovine trophoblast interferon inh ibits the production of the latent forms of matrix metalloproteinase-1 and -3 by ovine endometrial cells, and this is independent of its eff ect on prostaglandin production.