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Ovine trophoblast interferon modulates the secretion of a number of proteins 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 ovine endometrial cells and determined whether they are mediated via effects on prostaglandin synthesis. Both ovine trophoblast interferon (30 ng ml-1) and human recombinant interferon alpha (50 U ml-1) inhibited the production of latent matrix metalloproteinase-1 and -3 (P &lt; 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 PGE2 or PGF2 alpha (each 10 mumol l-1) either alone or in combination. Indomethacin (12 mumol l-1) similarly inhibited the production of latent matrix metalloproteinase-1 and -3, but production was partially restored by adding the prostaglandins either singly or in combination. PGE2 and PGF2 alpha together had no effect on enzyme production. These data were confirmed by gelatin and casein zymography. Northern analysis showed a 4.5-fold increase in the abundance of specific mRNA for latent matrix metalloproteinase-1 following treatment of cells with phorbol myristate acetate, but a marked decrease following interferon treatment. Thus, ovine trophoblast interferon inhibits the production of the latent forms of matrix metalloproteinase-1 and -3 by ovine endometrial cells, and this is independent of its effect on prostaglandin production.

Modulation of production of matrix metalloproteinases from ovine endometrial cells by ovine trophoblast interferon